E. A. Hessel, II:
Department of Anesthesiology and Surgery, University of Kentucky College of Medicine, Lexington, Kentucky 40536

The more extensive a man's knowledge, of what has been done, the greater will be his power of knowing what to do.

Benjamin Disraeli, 18041881

Those who cannot remember the past are condemned to repeat it.

Santayana, Life of Reason

Why examine our past? First, it tells us of our heritage, of how we got to where we are. Second, it helps us to appreciate what we have today and to place our practice in perspective. Third, it provides clues to the characteristics of successful persons and of the discovery process. Finally, it may inspire us to add to the rich history of our profession. "In the continual remembrance of a glorious past, individuals and nations find their inspiration" (Sir William Osler, 18491919).

Cardiac surgery is remarkably young, almost its entire history having occurred in slightly more than the past 100 years, and the most important advances within the lifetimes of currently practicing physicians. Many of the participants are still living or have left personal accounts of these events, and original publications are readily available. The reader may be surprised by how recent in origin are the procedures we take for granted today. In 1936, there was no known surgical treatment for congenital or valvular heart disease. In the spring of 1944, there was no surgical palliation available for cyanotic congenital heart disease. At the start of 1952, open cardiac surgery was not possible. At the start of 1960, there was no satisfactory prosthetic valve available, nor an implantable pacemaker, nor even closed chest massage; and infant heart surgery was very risky. In early 1967, direct coronary artery surgery was a rarity and saphenous vein bypass surgery was unheard of, as was human heart transplantation and surgical therapy for tricuspid atresia or hypoplastic left heart syndrome. Intraortic balloon pumping (IABP), cardioplegia, monitoring of heparin dosing, balloon-tipped pulmonary artery catheters (PACs), high-dose narcotic anesthesia, dopamine, dobutamine, and prostaglandin therapy were not yet available. In 1984, internal mammary artery grafting was not generally practiced, nor was monitoring by pulse oximetry, capnography, or transesophageal echocardiography (TEE). Propofol, aprotinin, amrinone, and adenosine were not available, and nitric oxide was only considered an environmental toxin.

Writing history is always subjective. The author makes decisions as to what is important and what should be included. There is also the problem of priority. Options include who first conceived of a procedure, who first attempted (but failed), who first successfully accomplished the procedure, who first published it, and who popularized the procedure. Often two or more surgeons accomplished a new procedure at almost the same time and possibly (it is often difficult to know for certain) independently and unaware of the other's work. In some secondary sources, the dating is confused because an author has used the date of publication rather than the date of the procedure. In this chapter, the latter was used and the original paper was consulted when there was ambiguity.

Although the history of cardiac anesthesia is inexorably intertwined with that of cardiac surgery, for this chapter the two are dealt with separately so as to emphasize the history of cardiac anesthesia, which has received little attention in the past.

The literature on the history of cardiac surgery is extensive. A number of books (13) and articles and book chapters (410), are useful, but the recent books by Harris B. Shumacker Jr., The Evolution of Cardiac Surgery (11), and by Stephen Westaby with Cecil Bosher, Landmarks in Cardiac Surgery (12), are exceptionally informative and are recommended to the inquisitive reader. The book by Shumacker, a pioneer in cardiac surgery, is thoroughly referenced and provides the insights of a surgeon who was there during most of its development. Westaby is a contemporary British cardiac surgeon; his book is richly illustrated and includes many biographic sketches, anecdotes, vignettes, personal impressions, and quotations from those involved, and well as reprints of 44 original articles of historical import. Unfortunately, it lacks all other references.

Table 1-1 lists some historical milestones in cardiac surgery, and Table 1-2 adds some of the important adjuncts to the development and progress of cardiac surgery. At the same time, other developments were occurring in cardiovascular medicine that had an impact on the practice of cardiac surgery and anesthesia, and some of the more notable of these are listed in Table 1-3.

18961928: first steps and dogma

Slightly more than 100 years ago, on September 9, 1896, Ludwig Rehn of Frankfurt first successfully sutured a stab wound of the heart (right ventricle) (11). Many consider this to be the beginning of cardiac surgery. Like all "firsts," this accomplishment followed essential work by others. Although operative drainage of pericardial fluid was first suggested by Jean Riolan in 1648, it was not accomplished until the early 1800s, by Francisco Romero of Barcelona and Baron Dominique Jean Larrey of France. In the early 1880s, Block of Danzig and Simplicio Del Vecchio of Italy reported the repair of experimental wounds of the heart (11). However, one of the most prominent surgeons of that time, Theodor Billroth, pronounced that "A surgeon who would attempt such an operation [cardiac suture] should lose the respect of his colleagues (7)." Unsuccessful attempts at suturing heart wounds in humans were made by Ansel Cappelen in Norway in 1894 and Guido Farina of Rome in 1896, and in that year Great Britain's Sir Stephen Paget predicted that "surgery of the heart has probably reached the limit set by nature to all surgery; no new method and no new discovery can overcome the natural difficulties that attend a wound of the heart" (7). That same year, Rehn accomplished the "impossible." On September 2, 1902, John H. Gibbon of Philadelphia operated on a moribund patient for a wound of the heart, but the patient died before the wound could be closed (11). Half a century later (1953) his son, John H. Gibbon Jr., would be the first to successfully conduct open heart surgery with the aid of a mechanical heart-lung machine. On September 14, 1902, Luther L. Hill of Montgomery, Alabama, first successfully sutured a cardiac wound in the United States (11). By 1907, Rehn reported 124 such attempts with 40% survival rate (7). This was accomplished in the era before endotracheal intubation, antibiotics, and blood transfusion!

Blood types were first identified by Landsteiner and others in 19001902, and blood typing before transfusion was introduced by Ottenberg in 1907. However, satisfactory anticoagulation of the blood with citrate (A. Hustin and L. Agote) and addition of glucose (Rous and Turner), so that it could be bottled and stored to make administration practical, was not introduced until 19151916 (3,48).

In 1902, Sir Lauder Brunton of St. Bartholomew's Hospital in London, emboldened by good results with surgical treatment of wounds of the heart and based on autopsy studies and animal experiments, published a paper in The Lancet suggesting the possibility of surgical treatment of mitral stenosis. He noted how incapacitating a condition this was and the fact that medical therapy could do nothing to relieve the stenosis. He observed that it was easy to separate the adherent cusps (i.e., fused commissures) at autopsy and advocated consideration of surgically splitting the valve along the adherent contact margins (a procedure later to be called commissurotomy) (87). However, his suggestion was met with strong disapproval in subsequent issues of The Lancet, including an editorial, which criticized his failure to completely study the problem experimentally, suggested that such an operation would probably prove fatal and that if it did not its benefits would probably be temporary, and finally pointing out that the prognosis of mitral stenosis depended as much on the condition of the myocardium as on the size of the mitral orifice (7,87). These criticisms stifled further work for the next 20 years.

In 1920, Elliott Cutler and C.S. Beck at the Peter Bent Brigham Hospital in Boston (Harvard), began experiments that led to the first successful operation for mitral stenosis, on May 20, 1923. Unfortunately, their operation was designed to relieve the stenosis by cutting the leaflet (rather than splitting the commissure), assuming that mitral insufficiency was less serious than mitral stenosis. They applied this ill-conceived (in retrospect) procedure in six subsequent patients, the last on April 15, 1928, but none of the patients survived (7,88).

There was one other successful mitral valve operation in that era, which was performed by Henry Souttar in London on May 6, 1925 (87). He use transatrial digital dilitationa technique that was resurrected by Brock in 1948 and became the standard procedure until it was largely replaced in the mid-1950s by transventricular dilitation using a mechanical dilator. Unfortunately, the patient was found to have considerable mitral regurgitation on initial exploration and benefited minimally from the procedure. However, Souttar was impressed with the information gained from the digital explorationan appreciation of the reality of stenosis and regurgitation, the mechanical nature of these lesions, and the practicability of their surgical relief (11). However, he did not get another opportunity, because "the physicians declared that it was all nonsense and that the operation was unjustifiable" (7). "It was an article of faith with physicians that the valves were of no importance and that the only thing that mattered was the condition of the cardiac muscle" (7). Successful conquest of mitral stenosis would have to wait 23 more years.

Other notable developments occurred in the first quarter of the 20th century. After extensive laboratory experimentation, Friedrich Trendelenburg of Leipzig first attempted a pulmonary embolectomy with normothermic inflow occlusion (the Trendelenburg procedure) in two patients in 19071908, neither of whom survived. Several others attempted this procedure without success until Martin Kirschner of Konigsberg, a student of Trendelenburg, finally succeeded on March 18, 1924 (11). By 1935 about 142 Trendelenburg operations had been reported, with only 9 hospital survivors (89). As described later, this operation played a pivotal role in the subsequent development of the first clinically successful heart-lung machine by John Gibbon Jr.

Following better understanding of the pathophysiology of chronic contrictive pericarditis elucidated by Norman Cheevers of London in 1882 and the German Friedel Pick in 1896, Ludwig Rehn of Frankfurt and Ferdinand Sauerbruch of Berlin both successfully performed pericardiectomies for this condition in 1913 (11). This procedure was applied extensively by Claude Beck of Cleveland, who, based on his observations of vascular adhesions between the pericardium and epicardium in clinical and experimental models of pericarditis, conceived of and developed his various operations to improve collateral blood flow to treat coronary artery disease between 1935 and 1941 (11).

19381948: closed heart surgery comes of age

The remarkable decade in which closed heart surgery became a therapeutic reality began on August 28, 1938, when a 33-year-old chief resident surgeon at the Children's Hospital in Boston successfully ligated a patent ductus arteriosus (PDA) while his chief, William Ladd, was away on his summer vacation. Robert E. Gross had prepared himself for this endeavor in the experimental laboratory and with 3 years of training in pathology (13,90). As is frequently the case in the history of cardiac surgery, another surgeon had missed the opportunity of this historic first the previous year. John W. Strieder almost obliterated an infected ductus arteriosus on March 16, 1937, in a young woman who did well until she died suddenly 5 days after surgery from acute aspiration after emesis caused by acute gastric dilitation (91).

In October 1944, Clarence Crafoord of Stockholm first successfully resected a coarctation of the aorta in two patients. This was followed by Gross' first success with the same operation in June 1945. Gross may have been unaware of Crafoord's work; both reports were published in the fall of 1945 (14,92).1

1For an interesting analysis of the reasons for the delay in development of an operation for coarctation and the competition between Robert Gross and Clarence Crafoord, see the article by Dobell (90).

Perhaps the most dramatic announcement came in 1945, when Blalock and Taussig of Johns Hopkins Hospital announced their successful creation of a systemic-to-pulmonary artery shunt to palliate tetralogy of Fallot, which was first accomplished on November 29, 1944 (15). The idea for this operation was that of Helen B. Taussig, Chief of Pediatric Cardiology. Although she was the daughter of a Harvard professor, Harvard Medical School did not accept women at that time, so she attended Johns Hopkins Medical School. Again because of her gender she could not obtain an internship at Johns Hopkins (the one position reserved for a woman was given to a classmate), and so she took a cardiology fellowship instead, and eventually was appointed director of the Pediatric Heart Clinic. In the course of caring for children with tetralogy of Fallot, she noted that those who also had a persistent ductus arteriosus did better until it closed off; it then occurred to her that other children with the tetralogy could be helped by surgical creation of a ductus. In about 19381939, she took her idea to the leading pediatric cardiac surgeon of that day, Dr. Gross, who allegedly replied, "Madam, I close ductuses, I do not make new ductuses" (10). Taussig had to await the arrival of Alfred Blalock as Chief of Surgery in 1941. Dr. Blalock had been a surgical resident at Johns Hopkins but was not offered a chief residency, so he went to Vanderbilt as their first Surgical Chief Resident and subsequently a faculty member. While there he had attempted (unsuccessfully) to produce pulmonary arteriosclerosis in animals by anastomosing the subclavian artery to the pulmonary artery. When Dr. Taussig approached Dr. Blalock with her idea of creating a ductus to treat tetralogy, Blalock's old experimental procedure came to mind. He then spent 2 years perfecting the operation in the laboratory and testing it in a cyanotic animal model before he was ready to attempt it in a patient in the fall of 1944. Much of the laboratory work was done by his Afro-American research associate, Vivan Thomas. The first clinical attempt was a success, and in the following year 55 patients underwent the Blalock-Taussig operation, with a mortality rate of 20%. By the end of 1950, they had operated on 1,037 patients, and the mortality rate had fallen to less than 5% (93).2

2For personal recollections of this momentous advance see the articles by Blalock (94) and Taussig (95). For a brief biography of Helen Taussig and her contribution to this operation, see the chapter by Nuland (93).

The first Blalock-Taussig operation was followed 2 years later by the side-to-side descending aorta-to-pulmonary artery anastomosis, performed by Willis J. Potts at the Children's Memorial Hospital in Chicago on September 13, 1946 (16), and the next year by closed pulmonary valvotomy, by T. Holmes Sellors on December 4, 1947 (17), and Russell C. Brock on February 16, 1948 (96), both in London.

Finally, the successful closed treatment of mitral stenosis (closed mitral commissurotomy) was accomplished in 1948after a latency of about 23 years since the work of Cutler, Allen, and Souttar and 46 years since Sir Lauder Brunton's suggestion was so soundly rejected. The year began with the efforts of H.G. Smithy of Charleston, South Carolina, who performed closed partial mitral valvulectomy (the old Cutler procedure) to palliate mitral stenosis in seven patients between January 30 and June 14, 1948, with five survivors, three of whom improved (97).3 On June 10, 1948, after four unsuccessful attempts (the fourth earlier that same day in another hospital), Charles P. Bailey of Philadelphia first successfully incised (with a blade) the fused commissure (and hence the term "mitral commissurotomy"); the female patient did so well that 1 week later he had her travel 1,000 miles by train to be presented at a meeting of the American College of Chest Physicians (19), and she remained well for the next 38 years (98). Dwight Harken, then at Tufts College Medical School in Boston, probably emboldened by his experience of removal of 96 foreign bodies from the heart during World War II (99), successfully incised (with a valvulatome) the commissures of a patient only 6 days later, on June 16, 1948 (20).4 Six of his first 10 patients died and he almost abandoned the procedure, but his cardiology colleague, Dr. L.B. Ellis, encouraged him to continue, and 14 of the next 15 survived (100). On September 16, 1948, R.C. Brock of Guys Hospital in London successfully accomplished a closed mitral commissurotomy using Souttars' original transatrial finger dilitation technique (101). This became the preferred method until Andrew Logan of Edinburgh introduced the use of the transventricular dilator (Tubbs) in 1954 (102). Logan's method was rapidly adopted as the preferred method of closed mitral commissurotomy and was commonly practiced (including by the author) until the late 1960s and early 1970s, at which time open mitral commissurotomy (i.e., on cardiopulmonary bypass) largely replaced the closed techniques. Transventricular mechanical dilitation was the immediate ancestor of transcatheter balloon dilitation of the mitral valve, which was introduced in the 1980s.5

3It is ironic that Smithy's career abruptly ended later that same year, when he died of aortic stenosis on October 28th at the age of 36 (12).

4Perhaps Dr. Harken may be excused if, 41 years later and at the age of 79, he incorrectly stated in his personal recollections the dates of his and Bailey's first successful mitral valve operations (100).

5For a more thorough review of the early history of mitral valve surgery, see the chapter in the book by F. Henry Ellis Jr., (88).

19521955: open heart surgery accomplished

Open heart surgery had not yet been successfully accomplished by the start of 1952. However, on April 15 of that year, Robert E. Gross at the Boston Children's Hospital successfully used his "atrial well" technique to close an atrial septal defect (ASD) (26). This ingenious technique consisted of sewing a soft, plastic, funnel-like device onto the wall of the right atrium, which was then entered. The surgeon was then able to digitally explore the atrial structures and perform a surgical repair working beneath the layer of blood in the well. This method precluded direct vision but in clever hands permitted remarkable results. Using this technique in 1954, Dr. John Kirklin at the Mayo Clinic successfully corrected a partial common atrioventricular (AV) canal (combined atrial and ventricular septal defects) (103).

On September 2, 1952, John F. Lewis and colleagues at the University of Minnesota successfully closed an ASD under direct vision during 5.5 minutes of circulatory arrest (caval inflow occlusion) permitted by moderate surface-induced hypothermia (26°C) (27). By February of 1954 they had used this method 11 times with only 2 deaths; 1 was a patient with a primum ASD who developed surgical complete heart block for which no therapy was then available (104). [Lillehei and colleagues at the University of Minnesota first used an epicardial electrical pacemaker to treat this complication on January 30, 1957 (54).] Henry Swan and colleagues at the University of Colorado also starting using hypothermia and brief periods of circulatory arrest and accomplished open repair of both valvular or infundibular pulmonic stenosis and ASD in 12 patients between February 19 and July 9, 1953, with only one death (105). This method, although it continued to be used for several years for surgical repair of these defects, had the obvious time limitation of about 8 to 10 minutes. There remained the need for a heart-lung machine to support the patient and permit the surgeon time to accomplish complex intracardiac repairs under direct vision. This leads to the remarkable story of John H. Gibbon Jr.6

6For a biography of John Gibbon and a detailed review of his development of the heart-lung machine, see the book by Romaine-Davis (106).

On October 3, 1930,7 during a 1-year surgical research fellowship (immediately after his internship) at the Massachusetts General Hospital under Dr. Edward D. Churchill (studying an animal model of pulmonary embolism), Dr. Gibbon was assigned the task of monitoring a young woman who had suffered a massive pulmonary embolism after a cholecystectomy. The patient was transferred to the operating room, where she was to be observed until she had deteriorated sufficiently to justify an attempt to perform a Trendelenburg operation (closed pulmonary embolectomy). He watched her all night. While observing her distended veins and cyanosis, it occurred to Dr. Gibbon that if he could only remove her venous blood, bypass her heart and lungs, oxygenate the blood and return it to her arterial system, she could be saved. But such technology did not exist, and the patient did not recover from the pulmonary embolectomy that was performed the following morning. Based on this experience, Dr. Gibbon made up his mind to try to develop a heart-lung machine. Over the next 3 years he reviewed previous work in this field and discussed his ambition with numerous colleagues, but no one seemed interested and most experts doubted its feasibility. However, he was not to be discouraged. He obtained a second year of research fellowship with Dr. Churchill in 19341935 and, together with his new wife Mary, who had been Dr. Churchill's research assistant, built a heart-lung machine. By the end of the year, they had supported cats for up to 171 minutes of total cardiopulmonary bypass (CPB) (89). He continued his research at the University of Pennsylvania and by 1939 was able to report long-term survivors among cats subjected to total CPB for 10 to 20 minutes (109). Despite interruption by 4 years of military service in World War II and continued skepticism by the medical community, Dr. Gibbon continued his work, now in collaboration with International Business Machines Corporation (IBM), and by the end of 1952 he had developed a heart-lung machine that featured a vertical screen oxygenator and was capable of supporting a human; with this machine he achieved almost 90% survival in dogs (110). Dr. Gibbon first used this heart-lung machine clinically in a 15-month-old child in February 1952, but she died during surgery because she had an undiagnosed PDA instead of the anticipated ASD. However, the next patient, an 18-year-old operated on May 6, 1953, had her ASD successfully closed during 26 minutes of full bypass and 45 minutes of total bypass (29,107,108). Thus after 23 years Dr. Gibbon achieved the goal he first conceived as a resident physiciana goal that had eluded many others. [It is intriguing that just 11 days earlier (April 25, 1953) another monumental development of the 20th century in biomedical science, the description of a proposed structure of DNA (the double helix), was announced by Watson and Crick (74).] Unfortunately, his next two patients, children 51/2 years old with ASD operated on in July of that year, both diedone of cardiac arrest before cannulation and the other of unsuspected coexisting ventricular septal defect (VSD) and PDA resulting in excessive blood in the field.8 Dr. Gibbon declared a moratorium on further use of his heart-lung machine. The fact that none of the other 12 attempts by five other groups to use total CPB up until this time had succeeded (111) tended to reinforce the attitude of hopelessness.

7This is the date stated by Gibbon's biographer, A. Romaine-Davis (106). Dr. Gibbon, in an historical review published in 1970 (107) and another submitted in 1973 (108), places this event in February of 1931.

8Cardiac surgeons soon learned that an unsuspected patent ductus would cause excessive blood flow into the field during CPB, and they began to routinely look for its presence (and ligate it if present) before proceeding to CPB. This problem can be encountered during adult noncongenital surgery and should be suspected with increased blood return to the left side of the heart (see Chapter 12).

On March 26, 1954, however, C. Walton Lillehei and his colleagues at the University of Minnesota initiated a remarkable series of direct-vision intracardiac surgery with total CPB using the patient's parent as the "heart-lung machine" (so-called controlled cross-circulation, in which the parent's femoral artery and vein were connected to the patient's arterial and venous system respectively (Fig. 1-1). Between March 1954 and July 1955, 45 patients were operated on using controlled cross-circulationincluding 27 patients with VSD, 10 with tetralogy of Fallot, and 5 with AV canalwith 28 survivors (111,112). In his discussion of the report of the first eight VSDs he had closed using cross-circulation Lillehei stated, "The demonstration that right ventricular cardiotomy and septal suture can be successfully performed even in seriously ill patients should dispel much of the discouragement previously prevalent in this field and stimulate further rapid developments in the application of direct vision intracardiac corrective surgery to congenital and acquired cardiac pathology" (31). Lillehei had clearly demonstrated the potential for CPB to permit major open heart surgery once a satisfactory artificial heart-lung machine was available to skillful cardiac surgical teams.

FIG 1.1. A depiction of the method of direct-vision intracardiac surgery using extracorporeal circulation by means of controlled cross-circulation used by C. W. Lillehei and his team at the University of Minnesota in 1954 and 1955.A:
The patient, showing sites of arterial and venous cannulations.
B:
The donor, showing sites of arterial and venous (superficial femoral and great saphenous) cannulations.
C:
The single Sigmamotor pump controlling precisely the reciprocal exchange of blood between the patient and donor.
D:
Close-up of the patient's heart, showing the vena caval catheter positioned to draw venous blood from both the superior and inferior venae cavae during the cardiac bypass interval. The arterial blood from the donor was circulated to the patient's body through the catheter that was inserted into the left subclavian artery.
[From Gravelee GP, Davis RF, Utley JR, eds. Cardiopulmonary bypass: principles and practice.Baltimore: Williams & Wilkins, 1993:10 (Fig. 1.2) with permission.]

This occurred at the Mayo Clinic (90 miles south of the University of Minnesota). There, under the leadership of John W. Kirklin, the first successful series of patients to undergo intracardiac surgery with the aid of a mechanical pump oxygenator (eight patients, four survivors) was undertaken between March and May of 1955; the heart-lung machine was a Mayo modification of the Gibbon-IBM model, the plans for which had been generously provided by Dr. Gibbon (32).9 This was followed by a series of seven cases done by Lillehei at the University of Minnesota (with five survivors), using a simple heart-lung machine of their own design employing a DeWall Bubble Oxygenator, between May 13 and August 9, 1955 (114).10 By the fall of that year these two institutions were regularly performing open heart surgery with mechanical heart-lung machines: Kirklin's group had done 40 cases, with 93% survival among their last 14 VSDs (116), and Lillehei's group had done 36 cases with 89% survival in their last 19 cases (114)! Over the span of 4 years the puzzle of open heart surgery had been solved, and many groups followed the next year.11 Comroe and Dripps (125) identified 25 bodies of knowledge that were required for the full development of open heart surgery.

9For a personal perspective on the beginning of open heart surgery at the Mayo Clinic, see the article by John Kirklin (113).

10For a personal perspective on the beginning of open heart surgery at the University of Minnesota, see the Chapter by C. Walton Lillehei (111) and the article by Warden (115).

11Others have more thoroughly reviewed the early history of the development of CPB (11,12,107,108,111,117122); Senning has reviewed its development in Stockholm (123) and Cooley its development in Houston (124).

As a footnote to the history of the development of the heart-lung machine, it is of interest to note that the first successful use of the machine to perform a pulmonary embolectomy was by Edward Sharp of Johns Hopkins Hospital (on February 17, 1961) and by Denton Cooley in Houston (on April 16, 1961), almost exactly 30 years after John Gibbon first set out to accomplish this goal (11).

In the last half of the 1950s, many groups initiated open heart programs employing CPB, mainly to treat congenital heart disease. A number of important developments occurred. Initially most open heart surgery was performed through a transverse sternotomy bilateral anterior thoracotomy with arterial cannulation of the subclavian artery. By the end of the decade, median sternotomy (55,56) and femoral artery cannulation (56) had replaced earlier approaches. (Why direct cannulation of the ascending aorta was avoided for another 15 years is not obvious). In 1957, Lillehei's group introduced temporary epicardial pacemaking to treat surgical heart block (54). In that same year, Sealy and others (57) introduced moderate hypothermia (approximately 30°C) produced by an efficient heat exchanger as an adjunct to CPB, initially to improve tolerance to low flows. Hypothermia was subsequently adopted by most teams to improve safety of organ preservation and tolerance of hemodilution. In 1959, Charles Drew of London introduced the technique of deep hypothermic (approximately 15°C) circulatory arrest (58).12 This was not widely adopted at the time but was reintroduced by David Dillard et al. at the University of Washington and by Brian Barratt-Boyes in Aukland, New Zealand, in the middle and late 1960s for facilitating infant heart surgery, and by Randall Griepp of New York in 1975 for conducting aortic arch surgery. At the end of this decade, Mason Sones at the Cleveland Clinic first accomplished selective coronary angiography (75)an innovation that would have profound impact on the future of adult cardiac surgery.

12For an interesting review of Charles Drew and his development of deep hypothermic circulatory arrest, see the article by Dobell (126).

The practice of surgery had been affected so greatly by the developments in cardiac surgery that in July 1959, "recognizing the great advances in cardiac surgery," the title of the Journal of Thoracic Surgery was changed to the Journal of Thoracic and Cardiovascular Surgery.

Although many ingenious palliative or reparative procedures for valvular heart disease had been introduced, for many patients a replacement device was needed. Many different devices were introduced with limited success. Even though moderately good short-term success was achieved with aortic valve replacement with prosthetic trileaflet valves (often made of uncoated or coated Teflon fabric or of silicone rubber) that imitated the natural valve, these usually failed after 1 to 2 years. The path to success was initiated by Dwight Harken in 1960 when he successfully replaced the aortic valve in two patients with a caged ball prosthesis implanted in the subcoronary position (35,127) and by Albert Starr of the University of Oregon, who successfully replaced the mitral valve in six of eight patients with a caged ball prosthetic valve between August 1960 and February 1961 (36). This valve was codeveloped with a retired engineer, M. Lowell Edwards (who had come to Dr. Starr in 1958 with a proposal to develop an implantable artificial heart, but who accepted the challenge to start on one valve at a time and ended up with his famous medical products company). Starr and Edwards then developed a caged ball aortic prosthesis featuring a flexible fixation (sewing) ring, which Dr. Starr successfully implanted in eight of ten patients between March and September of 1962 (128). For many years these Starr-Edwards valves were favored by many surgeons and were the standard against which subsequent valves were compared, having been implanted in more than 175,000 patients (12).

Dwight McGoon and his colleagues at the Mayo Clinic provided evidence of the steep learning curve and rapid and dramatic improvement of results with prosthetic replacement of the aortic valve. Their hospital survival rate increased from 45% in 1960 to 85% in mid-1963 (129) and achieved 100% in the first 100 patients in whom they implanted a Starr-Edwards valve in 1963 and 1964 (130)!

Other approaches to valve replacement were introduced but did not receive wide acceptance at the time. Unstented homograft aortic valves were first implanted in the subcoronary position by Donald Ross of London in July 1962 (131) and by Brian Barratt-Boyes of Auckland in August of that same year (132), and Ross introduced his pulmonary autograft procedure (in which the patient's own pulmonary valve was implanted in the subcoronary position of the aortic valve and the pulmonary valve is replaced with a homograft) in 1967 (133).13

13For a more through review of the development of cardiac valve prostheses, see the book by Lefrak and Starr (134).

A second great breakthrough of the 1960s was the introduction in 1967 of coronary artery bypass grafting (CABG), initially mainly using saphenous vein aortocoronary autografts. This was the first truly effective surgical treatment of coronary artery disease. Innumerable indirect operations had been developed to treat this disease and subsequently discarded because of minimal benefit, beginning with cervical sympathectomy by Jonnesco in 1916 and including the various operations devised by the American Claude Beck between 1935 and 1948 (epicardial abrasion, cardiomyopexy, coronary sinus occlusion, and arterialization of the coronary sinus with a vein graft attached to the descending aorta).14

14See a catalogue of these various procedures in Table 1 on page 2 in the review by Miller (135).

One of the less rational procedures was bilateral internal mammary artery (IMA) ligation, originated by Fieschi, Zoja, Casa-Bianchi, Battezzati, and others in Italy (11) and popularized in the United States by Glover in the late 1950s. This procedure was laid to rest in 1959 by the negative results of one of the first prospective double-blind clinical studies of a surgical procedure conducted by the group at the University of Washington (136).

The most used indirect technique for treating ischemic heart disease in the early 1960s was implantation of the IMA into the myocardium, a procedure developed by Arthur M. Vineberg of McGill University in Montreal. In 1946 Vineberg demonstrated development of anastomoses between the implanted IMA and the coronary arteries in dogs (137), and in November 1950 he successfully applied this procedure in a human (22). In 1958 he reported his results in 57 patients (138). However, few paid much attention until Sones in 1962 demonstrated, with angiography, coronary collateralization via IMA implants that had been placed 5 to 7 years previously in two patients (139). This led to the widespread application of the procedure. By 1968, the Cleveland Clinic had reported their results in 1,100 patients. An estimated 10,000 to 15,000 IMA implant operations had been performed by 1975, when the procedure was largely abandoned for the bypass procedure without ever having its efficacy conclusively resolved (140142).

Direct coronary artery surgery in humans began with the performance of coronary endarterectomy by Charles Bailey in October 1956 and by William Longmire and colleagues at the University of California, Los Angeles, in December 1957 (11). In 1963 Effler, at the Cleveland Clinic, modified the technique by eliminating the endarterectomy and simply opening over the stenosis ("endarterotomy") and applying a pericardial patch graft. The Cleveland Clinic used this operation in more than 140 patients between 1962 and 1967 (143). The revolution in direct coronary artery surgery began, however, in May 1967, when Rene Favaloro at the Cleveland Clinic first interposed a segment of saphenous vein (end-to-end and end-to-end) to relieve a stenotic right coronary artery and, before the end of that year, performed his first aortocoronary bypass graft to the right coronary artery (38,144).15 In 1968, three other groups began to do this procedureKerth and colleagues in San Francisco, Urchell and colleagues in Dallas, and W. Dudley Johnson and colleagues in Milwaukee16 (135). However, it was perhaps the presentation of Johnson in the spring of 1969 (40) that had the greatest impact on the widespread use of CABG using the saphenous vein. He suggested and demonstrated that CABG was applicable to most patients with coronary artery disease by placing multiple grafts distal to all disease and targeting the left anterior descending artery, branches of the circumflex, and the posterior descending coronary arteries in addition to the right coronary artery. He emphasized the use of CPB and intermittent aortic cross-clamping (15 minutes or less) to provide a dry, quiet field (40). These concepts revolutionized direct coronary artery surgery. In his prophetic discussion of Johnson's paper, Dr. Frank Spencer stated, "We may have heard a milestone in cardiac surgery today, because for years pathologists, cardiologists and many surgeons have repeatedly stated that the pattern of coronary artery disease is so extensive that direct anastomosis can be done in only 5 to 7 percent of patients. If the exciting data by Dr. Johnson remains valid . . . a total revision of our thinking will be required regarding the feasibility of direct arterial surgery for coronary artery disease" (40). Before the end of the decade more than 180 surgeons were doing CABG, and during the next few years the number of such procedures increased at a rate of 25% to 50% per year, to 54,000 cases in 1975 (135).

15An unsuccessful saphenous vein aortocoronary bypass grafting had been done by Sabiston in 1962, and successful grafts had been placed by Garrett and DeBakey in 1964 and by Kahn in 1966, but these were not reported until the 1970s (135) and had no impact on the introduction of CABG surgery.

16Johnson stated that he did his first aortocoronary saphenous vein graft in January 1968, after hearing of the work at Cleveland Clinic (145). Unlike the latter group, which initially did an end-to-end anastomosis between the saphenous vein and the distal coronary artery, Dr Johnson used an end-to-side anastomosis to the distal coronary artery, a technique that was subsequently adopted by the Cleveland Clinic group and most other surgeons.

In this same decade (1960s), an alternative graft was proposed for CABG, namely the IMA, usually used to anastomose into the left anterior descending coronary artery. This grafting was first successfully accomplished by RH Goetz et al., in the Bronx on May 21, 1960 (146) (without apparent further application), and then by Kolessov of Leningrad in 1964 (147) and Bailey et al. and Read et al. in 1968 (148). Interestingly, Kolessov performed his anastomosis off-bypass via a left thoracotomy, employed a 6- to 8-minute period of trial occlusion before isolating a segment of the coronary artery for performing the anastamosis, and administered sublingual nitroglycerin to his patients every 0.5 to 1 hour intraoperatively and postoperatively to prevent coronary artery spasm (149). After he presented his initial series (five of his first six patients survived) at the Cardiology Society plenum in Leningrad, the plenum adopted the resolution that "the surgical treatment for coronary artery disease was impossible and had no future" (147).

Despite these earlier efforts, it was primarily George E. Green of New York University who championed the use of the IMA graft in the United States. He emphasized the use of CPB and operating on the vented, fibrillating heart, sometimes arrested by aortic cross-clamping and administration of cold (lactated Ringer's solution) cardioplegia. He routinely used high magnification (16x) (41,150). (Interestingly, he never acknowledged the experimental or clinical work of others). Nevertheless, regarding the use of the IMA, Favaloro stated in 1970 that "It is highly doubtful that full clinical application of this procedure will reach a large scale" (139), and most other surgeons discounted or ignored this procedure because it was considered too difficult to perform, the IMA was considered to carry inadequate blood flow, or the operation was thought to be unnecessary. One who immediately recognized its potential, however, was another young surgeon at the Cleveland Clinic, Floyd Loop, who by late 1971 began to use the IMA (but without use of magnification) in significant numbers of patients [Loop, discussion of Green, 1972 (150)].

By 1980, fewer than 15% of surgeons used the IMA (151). This all changed in the mid-1980s, largely because of the long-term follow-up data provided by Loop and his colleagues at the Cleveland Clinic, who documented the dramatically improved patency of the IMA compared with the saphenous vein, especially beyond 5 years (152), as well as improved clinical outcome (153). By the end of that decade (1980s), most surgeons followed Loop's admonition that most patients with left anterior descending artery stenosis should receive an IMA graft whenever technically feasible (153).17

17Others have more thoroughly reviewed the history of the surgical management of coronary artery disease (8,135,144,147,148).

A third great landmark in cardiac surgery in the 1960s occurred on December 3, 1967, when Christiaan Barnard of Capetown, South Africa, performed the first human to human heart transplantation, described in the report on "The Operation," published in the December 30, 1967, issue of the South African Medical Journal (39). Unfortunately, the patient died 18 days after the operation. This accomplishment was the culmination of research that began with Alexis Carrel, the "father of vascular surgery" and 1912 Nobel laureate, who performed the first heterotopic heart tansplantation of a puppy's heart into an adult dog's neck. Further development involved many other researchers but especially the group at Stanford under Norman Shumway, who had achieved the first long-term survival (21 to 250 days) of dogs after orthotopically implanted homograft hearts. On January 6, 1968, Shumway's group did their first (and the world's fourth) human-to-human heart transplantation, following up on their extensive research program and initiating their remarkable innovative clinical program in heart transplantation. With inappropriate euphoria about 102 cardiac transplantation operations were performed during the next year by about 60 different teams in 20 countries (154,155). Most patients died as a result of the poorly understood problems of rejection and infection, and the procedure was abandoned by most groups, leaving predominately the Stanford group (Shumway) and a few othersLePetie Hospital in Paris (Cabrol), Grote Schurr Hospital in Capetown (Barnard), and Medical College of Virginia in Richmond (Lower)to carry on this experiment. It is noteworthy that Shumway, Cabrol, and Barnard had all studied under Lillehei at the University of Minnesota, and Lower had been a trainee of Shumway.18

18Others have more thoroughly reviewed the history of cardiac transplantation (156160).

Although the decade of the 1960s was marked by great strides in adult cardiac surgery, notable advances were also made in the treatment of congenital heart disease. An effective and readily applicable operation for transposition of the great arteries (TGA) was accomplished by William T. Mustard at the Hospital for Sick Children in Toronto on May 16, 1963 (interatrial venous transposition using a pericardial baffle, the so-called Mustard operation) (37). This work was the culmination of a career-long devotion of Dr. Mustard to achieving surgical correction of TGA. After extensive experimental work, in 1952 he attempted to treat TGA with a modified arterial switch operation (leaving the right coronary artery connected to the pulmonary artery) in seven children, using CPB employing a biologic (monkey lung) extracorporeal oxygenator (161). Unfortunately, none survived more than a few hours. This work had been preceded by the development of a palliative procedure for these babies (closed creation of ASD to improve mixing of pulmonary and systemic blood and, hence, improve systemic oxygenation) by Drs. Alfred Blalock and C. Rollins Hanlon of Johns Hopkins Hospital in 1948 (18). In 1957, K. Alvin Merendino at the University of Washington in Seattle almost succeeded in correcting TGA by conceiving of and applying the procedure of total interatrial venous transposition using a baffle made of compressed Ivalon sponge. One patient, operated on March 28, 1957, was alert and talking 3 hours after the operation when she suddenly became apneic, presumably from an air embolism, and died. This operation, except for the material used to construct the baffle, was identical to the subsequent Mustard procedure (162). In 1958, Ake Senning of Stockholm successfully corrected TGA in one of four children with his complex atrial correction using autologous (atrial) tissue (so called Senning operation) (34). Few surgeons could duplicate his success, whereas the Mustard procedure was readily accepted and successful in the hands of many surgeons. However, this procedure was usually done after 6 months to 2 years of age because of the high morbidity and mortality of neonatal surgery in that era, so it was usually preceded by a Blalock-Hanlon procedure. The latter was made obsolete in 1966 by William J. Rashkind of the Children's Hospital of Philadelphia with his balloon septostomy, the beginning of transcatheter or interventional cardiology (79).

In 19651967, Drs. David Dillard, K. Alvin Merendino, and Hitoshi Mohri at the University of Washington in Seattle introduced the technique of deep hypothermic (less than 20°C) circulatory arrest using surface cooling and warming without a pump oxygenator for conducting complex operations (e.g., total correction of total anomalous pulmonary venous return, AV canal, and TGA) in infants (60,163). The technique of Horiuchi et al. (164) of Sendi, Japan, had been introduced to the Seattle group by a surgical research fellow from Sendi, Dr. Ichiro Matano, who was working in their laboratory. The Seattle group, under the leadership of another research fellow from Sendi, Dr. Mohri, then modified the technique to permit deeper levels of hypothermia (less than 20°C) and longer duration of circulatory arrest (1 hour), allowing complex surgery (163,165). Deep hypothermic circulatory arrest became a mainstay of complex neonatal surgery for many years and is still practiced in some cases today. However, the pure surface technique of the Seattle group was not readily accepted, and deep hypothermic circulatory arrest did not become common practice until Brian Barratt-Boyes of Aukland, New Zealand, introduced his method in 19691970. Barratt-Boyes employed terminal perfusion cooling and rewarming with a pump-oxygenator (166). This also was a modification of a Japanese method of Hikasa et al. of Kyoto (167), and again it was introduced to Barratt-Boyes by visiting Japanese surgeons working in his unit in Aukland.

In the 1960s, CPB became common practice in many hospitals worldwide. Initially many employed Sigmamotor finger pumps, but these were quickly replaced with roller pumps, used by Michael DeBakey for transfusion of blood in 1934. Many employed homemade bubble oxygenators of their own design or copied from DeWall's design (114). In the late 1950s and early 1960s, the rotating disc oxygenator developed by Earle Kay and Fredrick Cross of Cleveland (168) became widely used, but it was subsequently displaced in many centers by unitized plastic disposable bubble oxygenators, such as the Travenol Mini Prime developed by Vincent Gott et al. at the University of Minnesota in 1957 (169), and later by hard shell bubble oxygenators with integral heat exchangers, such as the Bently Temprol Bubble Oxygenator developed by Richard DeWall et al. (170).

In this same decade some other "nonsurgical" developments occurred that were to have a major impact on the practice of cardiovascular medicine. On July 9, 1960, William B. Kouenhaven, a retired electrical engineer, and his colleagues at Johns Hopkins University introduced closed-chest cardiac massage (77). [They discovered the technique serendipitously when they observed an elevation in arterial pressure after the application of external defibrillator paddles to dogs (145)]. On June 6, 1960, William M. Chardack and Wilson Greatbatch, an engineer, implanted the first totally implantable, long-term, battery-powered pacemaking system (76). The unit was subsequently manufactured by Medtronic of Minneapolis. The leads were initially placed epicardially via a thoracotomy, but soon they were placed transvenously, following the work of Parsonet et al. (171) and Siddons et al. (172). The early pacemakers were asynchronous and were used exclusively to treat complete heart block. In 1966, Victor Parsonett et al. of Newark, New Jersey, described implantation of the first implantable R-wave inhibited demand pacemaking system (173). In 1965, Myron Wheat Jr. of Gainesville, Florida, introduced his nonsurgical management of dissecting aortic aneurysm using "anti-impulse" and antihyhypertensive therapy with the use of the antiadrenergic drugs trimethaphan, reserpine, and guanethidine (78). The idea germinated from information communicated to him by colleagues in the Departments of Pharmacology and Veterinary Science, who told him that certain flocks of turkeys were plagued by dissecting aneurysms and that the incidence of this poultry industry problem had been dramatically reduced by the addition of reserpine to the turkeys' feed (78,145).

In June 1967, Adrian Kantrowitz of Brooklyn, New York, first successfully treated a patient with cardiogenic shock with an IABP (80,174). Fifteen years earlier Kantrowitz and his brother Arthur, an engineer, had first introduced the concepts later to be known as "counterpulsation," and in 1961 Spyridon Moulopoulos, Steven Topaz (an engineer), and Willem Kolff of the Cleveland Clinic had conceived of accomplishing this with an IABP (175). Kantrowitz was the first to use it successfully clinically and then to report his dramatic results in a series of 27 patients (174). This was the first successful circulatory assist device, and it was rapidly adopted into the practice of cardiovascular medicine and surgery, where it continues to be applied to this day.19

19For a more detailed history of the IABP, see the chapter by Dehmer et al. (175).

19701980: more advances

Cardiac surgery was maturing in the 1970s. Perhaps the most notable advance was the introduction of cold potassium cardioplegia and its rapid and widespread acceptance and application in daily practice. In the United States this innovation is commonly attributed to William Gay Jr. and Paul Ebert (62), although numerous workers in many countries were involved in the development and modification of cardioplegia techniques. Although the use of higher concentrations of potassium to induce cardiac arrest were first proposed and used by Melrose, Sealy and Young, and others in the 1950s, the concept of administering much lower concentrations of potassium added to ice-cold electrolyte solutions in large quantities to not only induce arrest but preserve myocardial function was largely novel and quickly replaced other more cumbersome or less reliable techniques. The latter included ischemic arrest (which led to the discovery of ischemic contracture, the so called "stone heart"), topical hypothermia, and continuous coronary perfusion with blood (so effectively practiced by McGoon and his colleagues at Mayo Clinic). An illustration of the explosive acceptance of cold potassium cardioplegia is that in 1975 fewer than 6% of surgeons were using it during CABG, whereas by 1980 almost 92% were employing it (151).20

20Others have more thoroughly reviewed the history of cardioplegia and given appropriate credit to the many other contributors to this major change in the conduct of cardiac surgery (176179).

With improved CPB technology and increased use of deep hypothermic circulatory arrest, infant and neonatal surgery became more successful. In 1975 both Adib Jatene in Sao Paulo (May 8, 1975) (43) and M.H. Yacoub in London (October 30, 1975) (180), apparently independently, succeeded with the anatomic correction ("arterial switch") of transposition of the great vessels, and over the next 10 years this procedure gradually replaced Mustard's operation. The successful implementation of the arterial switch operation was made possible by the application of deep hypothermic circulatory arrest, surgical experience with microvascular techniques that grew out of the development of CABG, the introduction of optical magnification, and the availability of fine monofilament suture material (e.g., Prolene). In the latter part of the same decade, William Norwood of the Boston Children's Hospital developed and successfully applied the first stage of his innovative approach to the problem of hypoplastic left heart syndrome (44). However, one of the most important advances in neonatal cardiac surgery was nonsurgical: the introduction in 1976 by Peter Olley et al., of the Hospital for Sick Children in Toronto, of the use of prostaglandin infusions to maintain the patency of the PDA and, hence, improve oxygenation in neonates with ductal-dependent cyanotic heart disease (66). This largely eliminated the need to emergency cardiac surgery, but more importantly it greatly improved the physiologic condition of these infants when they did come to the operating room (just as had Rashkind's balloon septostomy a decade earlier). This pharmacologic therapy also led to the realization of Helen Taussig's thoughts of 40 years before, that if a method to "prevent the closure of the ductus" could be found "it would be a benefit to cyanotic infants" (95); in that earlier time, she was forced to simply urge her surgical colleagues to create a new ductus.

Notable innovations in prosthetic valves occurred during this decade (134). In the early 1970s, Viking Bjork of Sweden introduced his tilting disc prosthesis (181,182), which became very popular until it was largely supplanted by the St. Jude bileaflet (pyrolytic carbon) valve, which was first implanted the late 1970s and began to be widely used in the 1980s (183). Stent-mounted, glutaraldehyde-preserved heterograft (porcine) valves developed by Alain Carpentier of Paris in the late 1960s became available in the 1970s, first produced commercially by Warren Hancock (184), and bioprotheses began to compete successfully with mechanical valves. In 1976 Shiley laboratories began producing Marion Ionescu's stented valve, which was constructed from glutaraldehyde-preserved bovine pericardium (185).

Two other important innovations of the 1970s that had significant impact on cardiac surgery (and anesthesiology) were nonsurgical. The first occurred in 1970, when H.J.C. Swan, William Ganz, and colleagues at the Cedars-Sinai Medical Center in Los Angeles introduced their balloon-tipped flow-directed PAC (developed in association with and supplied by Lowell Edwards' company) (61). The second was announced in a one-page letter to the editor of The Lancet on February 4, 1978, from Andreas Gruntzig of Zurich, who described the first five successful procedures of transluminal dilitation of coronary artery stenosis (percutaneous transluminal coronary angioplasty, or PTCA), performed between September 16December 20, 1977 (81). As is said, "the rest is history."

Substantial progress in CPB technology was made in the 1970s. Highly efficient, disposable hard shell bubble oxygenators with integrated heat exchangers were introduced by several different manufacturers, including Bently, Harvey, Shiley, and Cobe. Clinically effective disposable membrane oxygenators were introduced by Lande (Edwards Laboratory) and by Kolobow (Sci Med) in the early 1970s, but they were mainly relegated to use in extracorporeal membrane oxygenation (ECMO) to treat respiratory failure. In about 1975, the use of membrane oxygenators for CPB received a boost with the introduction of microporous polypropylene membranes (e.g., Travenol TMO), but by the end of the decade membrane oxygenators were being used in fewer than 20% of cases (186). Microembolization during CPB became recognized as a potentially significant problem, and with it came the introduction of microfiltration. However, one of the most important innovations in CPB technique in this decade was brought about by two papers published in 1975 by Brian Bull (a pathologist) and his colleagues at Loma Linda University in California, who pointed out the limitations of existing heparin protocols and advocated the use of an objective monitor of heparin effect (and its reversal by protamine): the activated clotting time (64,65). Until that time heparin had been administered by various dosing schedules based on the patient's weight and duration of CPB without any monitoring of its effectiveness! Bull's recommendation was quickly adopted by many cardiac surgical teams, and by the end of the decade most used some type of objective monitoring and control of heparinization.

Throughout the 1970s only about 30 heart transplantation operations were being performed per year, and many of these were done at Stanford with new innovations and improved results (187). In 1973 the Stanford team introduced transvenous endomyocardial biopsy (63), which greatly improved the accuracy of diagnosis and hence the treatment of rejection. Between 1968 and 1978 the 1-year survival rate among their heart transplantation patients rose from 22% to 65% (157). In 1970, soil samples from the Hardanger Vidda region of Norway were sent to the Sandoz Laboratories, from which the fungus Tolypocladium inflatum was isolated. It produced metabolites with weak antifungal properties, but in 1972 Jean-Francois Borel determined that one extract had potent immunosuppressive properties. This was cyclosporin A, the first agent to act selectively on lymphocytes (159). After encouraging results in experimental heart transplantation, the Stanford group began using cyclosporin clinically in December 1980 (67). Between 1980 and 1985 their 1-year survival rate after heart transplantation increased from 63% to 83%, and the 3-year survival rate climbed from 52% to 70%.21 This led to a renewed interest in cardiac transplantation, and in 1981 more than 100 such operations were done in a single year, for the first time since 1968. By 1985 ten times that many were done, and by the end of the decade more than 2,400 were performed in a single year worldwide, in more than 200 centers (189). On March 9, 1981, the Stanford group performed the first successful heart-lung transplantation (190); on November 1, 1984, Denton Cooley of Houston performed the first infant (8-month-old) heart transplantation (46); and 1 year later on November 20, 1985, Leonard Bailey of Loma Linda University in California performed the first successful heart transplantation in a neonate (4 days old) (47).

21For a summary of the remarkable clinical experience with cardiac transplantation at Stanford University, see the article by Robbins et al. (188).

Previously mentioned developments in the 1970s (i.e., PTCA and the use of the IMA) had a major impact on the practice of coronary artery surgery in the 1980s. In 1982, the first total artificial heart was implanted by the group at University of Utah (45). Although this procedure did not work out for its intended purpose, it spurred the development and use of more powerful ventricular arrest devices (compared with the IABP) to treat temporary postoperative cardiac dysfunction and as bridges to heart transplantation. Along with PTCA, there was a beginning growth of interventional catheter-based cardiology, including balloon dilitation of pulmonary artery and valve stenosis, coarctation, and aortic and mitral stenosis; closure of PDA; and attempts at closure of ASDall designed to reduce the need for conventional cardiac surgery (8284). On the surgical side, with a more realistic appreciation of the limitations of prosthetic valves, there was a resurgent interest in repair rather than replacement of the mitral valve, especially for mitral regurgitation. This redirection was spearheaded and popularized by Alain Carpentier of Paris, whose work started in the 1970s but began to be widely practiced in the 1980s. Carpentier's introduction of the use of annuloplasty rings facilitated relief of mitral regurgitation in most surgeons' hands (191,192).

Major advances in understanding and improvements in the application of CPB occurred in the 1980s. In 1981, John Kirklin's group at the University of Alabama called attention to the systemic inflammatory reaction induced by CPB as a cause of much of the morbidity associated with cardiac surgery (193); this led to extensive and ongoing investigations into the nature, causes, and ways to modulate the incidence and effects of the inflammatory reaction. Increased interest in the neurologic consequences of CPB was spurred by reports in 1983 of measurements of cerebral blood flow during CPB in humans by L. Henricksen et al. in Copenhagen (194) and by the group at the University of Alabama (195,196). This was followed by more objective and sophisticated studies of the incidence of neurologic and neuropsychometric abnormalities after CPB. The group at Stanford emphasized the potential advantages of alpha-stat management of carbon dioxide and pH levels in arterial blood during hypothermia (197), and by the end of the decade this approach had been adopted by most groups (before that time, most groups employed pH-stat management, which often required the addition of carbon dioxide to the oxygenator). With the development of more efficient membrane oxygenators, and especially with the introduction of hollow fiber technology, the use of membrane oxygenators increased from 20% to 90% during this decade (and to 99% by 1994) in the United States (186). Probably spurred by their use in ECMO and as ventricular assist devices, centrifugal pumps began to supplant roller pumps as arterial pumps during CPB. After the serendipitous discovery of unusually "dry" surgical fields while investigating the use of high-dose aprotinin to reduce the inflammatory response during CPB (198,199), Dave Royston, Willem van Oeveren, Ben Bistrip, Steven Westaby, and others of London and the Netherlands first reported in 1987 the hemostatic benefits of aprotinin for cardiac surgery (68,69). In a few short years, the use of aprotinin or the synthetic antifibrinolytics became ubiquitous in the practice of cardiac surgery. It is of interest that the original characteristic (antiinflammatory) which led to the experiments that revealed aprotinin's hemostatic benefits has now become an additional rationale for the use of aprotinin during CPB.

19901999: more for less

The face of cardiac surgery in the 1990s, at least in the United States, was greatly influenced by changes in medical economics and in the "business of medicine" that resulted from the efforts of the Federal government and medical insurance companies to reduce the cost of medical care, the rise in managed care, the commercialization of medical practice, and the open competition among hospitals and practitioners. This contributed to the development of "fast-tracking," the marketing of "minimally invasive" cardiac surgery, and public review and oversight of the surgical results. In New York state, the public disclosure of the results of individual surgeons and hospitals began in 1991 (200)so called "report-card medicine" (201). This was facilitated by the development of risk stratification systems by the Veterans Administration Hospitals, the Society of Thoracic Surgeons, the Cleveland Clinic, and others in the late 1980s and early 1990s (202), and it had a laudatory affect on the outcome in some regions where hospitals worked together to compare results and help one another improve outcomes [e.g., the Northern New England Cardiovascular Disease Study Group (203)].

Minimally invasive surgery, which includes operating through smaller incisions instead of the usual full sternotomy, performing CABG off-bypass (either through small thoracic incisions or via a median sternotomy), and use of the proprietary Port Access System (Heart Port, Redwood City, CA) has become common practice despite limited objective data to support its benefit in terms of outcome.

Stentless valves were first implanted in 1987 by Dr. Tirone David of Toronto (204); results are beginning to suggest improved left ventricular function and structure, and these devices are receiving more widespread use despite technical demands. Whether they prove to be a better solution to valve replacement remains to be seen.

As pediatric surgeons applied more complicated surgical interventions in smaller infants, concern about the adverse neurologic consequences of prolonged periods of deep hypothermic circulatory arrest were raised, especially by the groups at Boston Children's Hospital (205,206) and Duke University (207). This led to efforts to improve the methods of conducting deep hypothermic circulatory arrest, such as duration of cooling and management of pH, partial carbon dioxide pressure (PCO2), and hematocrit, or to replace circulatory arrest with low-flow CPB. In 1990 the group at the Hospital for Sick Children in London introduced the use of modified ultrafiltration in infant surgery to reduce fluid overload and possibly to remove inflammatory mediators (71).

Other means to decrease the inflammatory and hematologic effects of CPB were introduced, including the use of heparin-coated circuits in 1990 (70) and the use of leukocyte-removing filters. These methods, as well as modified ultrafiltration, were outgrowths of the interest and studies of the inflammatory response to CPB that began in the previous decade. The merits of these efforts are discussed elsewhere in this book and probably await further investigation. Other refinements or developments in CPB introduced in the 1990s included the use of augmented venous return and the resurgence of "warm bypass" and "warm heart surgery," spearheaded by the surgeons in Toronto (208,209). The advent of warm bypass led to recognition of the potential dangers of cerebral injury from overheating and reassessment of the need, hazards, and benefits of hypothermia, which had been a part of cardiac surgery for almost 50 years. With the continued concern about the neurologic consequences of CPB, in 1992 the Washington University group called attention to the possible role of ascending aortic atherosclerosis and various surgical manipulations involving the ascending aorta and the diagnostic value of ultrasonic interrogation. They suggested ways to modify surgical technique to reduce these risks (72,210). In another area of cerebral protection, the technique of retrograde cerebral perfusion (originally introduced by Mills and Ochsner in 1980 to treat cerebral air embolism) was reintroduced in 1990 by Ueda and colleagues in Japan to improve cerebral tolerance to deep hypothermic circulatory arrest during aortic arch surgery (211). This technique has rapidly gained in popularity, although its benefits are yet to be conclusively proven, as discussed elsewhere in the book.

In the early 1990s, inhaled nitric oxide was added to the armamentarium in treating pulmonary hypertension, although its impact on ultimate outcomes is still being elucidated (73). In fact, the role of excess endogenous nitric oxide in producing adverse effects and its modulation may prove to be more important in the future than the addition of nitric oxide to inhaled gases.

The early pioneers in cardiac surgery readily acknowledged the important role played by the anesthesiologists. In his first paper on the systemic-to-pulmonary artery shunt, Blalock mentioned by name the anesthesiologists involved in each case (15), as did Potts (16) and Sellors (17) in their early case reports. In his Harvey Lecture, delivered in November 1945, Blalock offered as proof of the skill of the anesthesiologists who worked with him, Drs. Lamont and Harmel, "that there have been no deaths during the operation on the 55 patients" (94). In referring to his aorta-pulmonary anastamosis operation, Potts stated that "in an operation of this type, expert anesthesia is essential." But perhaps Russell C. Brock (later Lord Brock) expressed it most eloquently in his Alexander Simpson-Smith lecture, given at the Medical Society of Lon don on June 15, 1949, while discussing closed surgery for tetralogy of Fallot: "It is a type of surgery that is not for the lone operator. . . . Teamwork is of course essential in the operating theatre, where in addition to the surgical and nursing assistants, the aneaesthetist plays a part of fundamental impor tance which deserves a special tribute" (212). On the other hand, the role of anesthesiology in the development of cardiac surgery was virtually ignored in two recent exhaustive books on the history of cardiac surgery authored by Shumacker (11) and Westaby (12).

Little has been written on the history of cardiac anesthesia. Although Meade addressed a section on anesthesia in his book, A History of Thoracic Surgery, cardiac anesthesia was not mentioned (1). Keown, in the 1963 edition of his textbook on cardiac anesthesia (213), and Lake, in her textbook on pediatric cardiac anesthesia (214), included brief chapters on the history of cardiac anesthesia, and Arens (215) and Wynands (216) have written articles on the subject. The latter, written by one of the pioneering cardiac anesthesiologists in North America, is a rich review that emphasizes the contributions of Canadian anaesthetists and contains numerous personal memories of the participants as well as of the author. Finally, Arthur Keats, another one of the pioneers in the development of this subspecialty, reflected on his personal perspective on its development in his 1983 Rovenstine Lecture (217). For further information this author has had to search through the cardiac surgery and anesthesia literature and his own personal recollections, leaving much to be desired.

In Table 1-4 are listed some of the notable developments and contributions in cardiac anesthesia.

Early developmentsanesthesia for thoracic surgery

Before cardiac surgery (and hence cardiac anesthesia) could begin, fundamental advances in supporting patients during thoracic surgery had to be accomplished. This history of thoracic anesthesia has been thoroughly reviewed by L. Renhdell-Baker (246) and, to a lessor degree, by Meade (1) and Johnson (3). Of course, the pivotal advance was the introduction of anesthesia itself in the late 1840s. However, the next major challenge to thoracic surgery was how to ventilate the patient when the chest was open. Some ingenious approaches were explored, such as placing the patient's head in a positive pressure box [Brauer (1904) and Murphy (1905)] or operating within a negative pressure chamber with only the patient's head outside [Sauerbruch (1904)]; for a while, even into the 1940s, positive-pressure ventilation via a tight-fitting mask was used, particularly for children. The solution, however, was endotracheal ventilation. The first elective oral endotracheal intubation for anesthesia was performed by the Scottish surgeon, William Macewan, in 1878. In 1888, the American surgeon, Joseph O'Dwyer, designed metal endotracheal tubes with a conical tip to occlude the larynx and added a bellows device to provide posi tive-pressure ventilation. This was first used and advocated as the best means of preventing pulmonary collapse during thoracic surgery by the surgeon Rudolph Matas of New Orleans in about 1899. In 1919 Ivan Magill of Britain introduced blind nasal endotracheal intubation using red rubber (Magill tubes), and in 1926 Arthur Guedel of Indianapolis introduced cuffed endotracheal tubes. Although direct- vision, laryngoscope-aided intubation was slowly adopted in the 1920s, the Miller and Macintosh blades were not introduced until the early 1940s.

In 1924 Ralph Waters at the University of Wisconsin introduced his to-and-fro carbon dioxide absorber using soda lime granules. This was favored by many cardiac anesthesiologists until the mid-1950s, although Brian Sword introduced a circle system with valves and an in-circuit carbon dioxide absorber, removing the cannister from the patient's face, in 1930. Ayre introduced his T-piece in 1937, and G. Jackson Rees his modification in 1950.

The first important new anesthetic agent after ether, chloroform, and nitrous oxide was cyclopropane, which was introduced to clinical anesthesia by Ralph Waters in 1933 and was adopted by many cardiac anesthesiologists as an induction if not a maintenance agent. Its major drawback was its inflammability, which led to its ready replacement when halothane became available in the late 1950s. In 1952, Lucien Morris invented the Copper kettle, which permitted more precise quantitation of anesthetic dosing, and later in that decade the temperature-compensated agent-specific vaporizers (TEC) were introduced by Cyprane Limited of England.

In 1934, John Lundy of Mayo Clinic introduced thiopental into the practice of anesthesia, and for many years it was used for both maintenance and induction. In 1942, Griffith and Johnson of Montreal first used curare, and Stephens used it to facilitate thoracic surgery in 1947. Succinylcholine became available in 1949.

Although mechanical ventilators were developed as early as 1907 (the Draeger Pulmotor), and Crafoord introduced his commercially available Spiropulsator in 1940 and Blease the "pulmoflator" after World War II, the use of ventilators in the operating room was not readily accepted until the late 1950s. "Modern" ICU-type ventilators (e.g., Bennett, Bird) did not appear until the 1960s.

In 1894, Harvey Cushing advocated the recording of pulse rate on an "anesthetic record," and in 1901, he added cuff blood pressures (247).

Although a few recovery rooms were established before World War II and an Anesthesia Study Commission report published in 1947 suggested that they could improve outcome, recovery rooms did not become common until the mid-1950s, and surgical intensive care units, greatly spurred by the advent of open heart surgery, not until the early 1960s (248).22

22The author acknowledges the informative chapter by the late Rod K. Calverley for much of this background on the development of anesthesiology (249).

Early cardiac anesthesia

Little is known about the anesthesia provided during early cardiac surgical operations. Ellis, in 1975 (87), reviewed the anesthetic management of Dr. Souttar's patient who underwent mitral commissurotomy in 1925. He stated that anesthesia was administered by a surgeon, Eric Lindsay [although in a letter written to Brian Blades 30 years after the event, Dr. Souttar gives credit to his anaesthetist, Dr. John Challis (7)]. The patient was premedicated with morphine and atropine; induced with a combination of absolute alcohol, chloroform, and ether (ACE); and maintained with ether administered via an endotracheal catheter (? endotrocheal tube), and apparently breathed spontaneously throughout the procedure. Blood pressure was monitored about every 5 minutes (presumably noninvasively).

In 1994, Dobel outlined the anesthetic management of the patient in whom Dr. Gross first ligated a PDA in 1938 (90). Anesthesia was provided by a nurse anesthetist (Betty Lank), who used a tight-fitting adult mask that was shrunk (with alcohol) and strapped to the child's face. Monitoring included a finger on the superficial temporal pulse. The anesthetic agent used was cyclopropane. Blood was available but was not needed (13). For Crafoord's first coarctation repairs, accomplished in 1944, anesthesia consisted of a mixture of cyclopropane and nitrous oxide administered via an airtight endotracheal tube using controlled ventilation provided by a Spiropulsator respirator (14).

Between 1946 and 1950, the first papers on cardiac anesthesia appeared, reviewing the challenging experience of providing anesthesia for severely cyanotic and debilitated children undergoing systemic-to-pulmonary artery shunt operations (218,250253). Again the words of Lord Brock came to mind: "[These operations] involve considerable anxiety [and] demand the work and attention of an enthusiastic, loyal, and courageous team" (212). It is hard to underestimate the anxiety produced in contemplating anesthetizing for the first time one of these almost moribund children (who often had virtually no exercise tolerance, were bedridden, and suffered repeated hypoxic spells) for this radically new operation. Common themes in these reports included heavy premedication (morphine and scopolamine), induction and maintenance with cyclopropane (with or without a little ether), endotracheal intubation (a few tried mask-only ventilation early in their experience but quickly abandoned it for endotracheal intubation because of problems with maintaining ventilation, despite the concerns about postintubation airway problems in children). Most used controlled ventilation (with or without use of curare). The Waters to-and-fro carbon dioxide absorbing canister closed system was usually used. Monitoring methods were not detailed, nor was fluid management discussed except to warn against fluid overloading. Usually a cannula was placed in the saphenous vein of an ankle, and plasma was administered. In H.M. Harmel and Austin Lamont's report of Blalock's first 103 cases at Johns Hopkins Hospital (patients 10 weeks to 20 years old), the mortality rate was 23% (218). In William McQuiston's report of Potts and Smith's first 236 shunt cases at Children's Memorial Hospital in Chicago, the overall mortality rate was 13%, but that among the 135 patients aged 3 to 16 years in whom a shunt was actually constructed was only 3% (253). These remarkable results were achieved without the benefit of electrocardiographic (ECG) monitoring, arterial and central venous lines and monitoring, pulse oximetry, and end-tidal carbon dioxide monitoring; modern inhalation agents, narcotics, muscle relaxants, and antibiotics; intensive care units, or even recovery rooms. In May 1948, the Chicago group began using mild surface-induced hypothermia ("refrigeration"; rectal temperature, 92° to 93°F) in these cyanotic children and observed decreased incidences of cerebral hypoxia and cerebral death (2% and 1.5%, respectively, compared with 7% and 4% in historical controls) in shunted patients and a reduced mortality rate (14% versus 54%) in those in whom a shunt could not be constructed (253). This was the first clinical use of hypothermia in cardiac surgery, a technique which would reappear on many occasions in the future. Alvin Harris in San Francisco described a somewhat different anesthetic technique in 25 children; he used rectal Avertin (tribromethanol) to induce basal narcosis and maintained the patients with nitrous/oxygen, curare, and morphine sulfate (later to be called "balanced anesthesia") (251). However, this technique did not appear to be well accepted at that time (254).

Robert M. Smith of Boston Children's Hospital (254) and E.M. Papper and Thomas McDermott at Babies Hospital in New York City (255) reviewed the pathophysiology and anesthetic management of patients with ductus arteriosus, coarctation of the aorta, pulmonic stenosis, vascular rings, or tetralogy of Fallot. Papper and McDermott emphasized the benefits of endotracheal intubation [although M.H. Adelman reported his successful use of mask ventilation during surgery for PDAs (256)]. By 1950, the Boston Children's Hospital group (Gross and Smith) reported a mortality rate of 1% in 455 children with PDA and 8.5% in 155 with coarctation (254). The Chicago group (Potts and McQuiston) reported the results in their first 1,000 operations for congenital heart disease as of February 1955 (257): the mortality rate in surgery for isolated pulmonic stenosis (61 patients) was 1.6%, for PDA (347 patients) it was 0%, and for coarctation of the aorta (52 patients) it was 4%. Again, these results were achieved without the "benefits" of modern anesthesia technology.

Between 1951 and 1955, the first papers on providing anesthesia for mitral commissurotomies were published (220,258262). Moderate premedication including phenobarbital and morphine or meperidine was usually recommended. All groups emphasized the importance of using the lightest possible anesthesia but employed different agents to accomplish this goal. An extreme example of light anesthesia was the technique of C.E. Wasmuth at the Cleveland Clinic. He used nitrous oxide (80% to 50%) in oxygen, supplemented with small amounts of thiopental, morphine, or demerol and local infiltration of the intercostal incision, and insisted that the patients respond to questioning throughout the procedure (although they denied pain and had no recall!) (259). All groups employed endotracheal intubation, often with topical anesthesia, but there was considerable controversy as to whether ventilation should be merely assisted (to avoid the possible negative impact of controlled ventilation on right ventricular function) or controlled, and on the pros and cons of using muscle relaxants such as curare (260) or infusions of succinylcholine (262). Two authors recommended use of mechanical ventilators to provide reliable ventilation and "free up the anesthesiologist's hands for other exceedingly important duties" (259,260). [The Swedes had been using ventilators during cardiac surgery since the late 1930s (14).] In the earliest report Kenneth Keown, who worked with Charles Bailey, advocated running an infusion of procaine throughout the case to reduce arrhythmias (220), but this approach was not adopted by most subsequent authors. Continuous ECG monitoring was employed by all, some using an oscilloscope (258,259). All started large-bore intravenous access and had blood available, including blood pumps and means of giving intraarterial transfusions, but all emphasized the need to minimize fluid and blood administration to avoid fluid overload. Keown (220) even advocated removing the venous cannula at the end of the case (if the patient was stable) "to avoid the temptation to give excessive fluids." All patients were extubated at the end of the case but given supplemental oxygen postoperatively. Several groups employed paravertebral or intercostal nerve blocks for postoperative anlagesia. All authors emphasized the need to move or change the patient's position slowly and gently while the patient was still under anesthesia or emerging, to avoid hemodynamic instability.

Perhaps an even more daunting task was the provision of anesthesia for patients with severe aortic regurgitation who were undergoing insertion of a prosthetic ball valve prosthesis in the descending aorta by Dr. Charles Huffnagel of Georgetown University (without benefit of left heart or cardiopulmonary bypass). This was first performed in September 1952 (25). The anesthetic management of these patients was described by John A. O'Donnell and Thomas F. McDermott in 1955 (263). All 42 patients were in medically irreversible congestive heart failure, and 40% had intractable angina pectoris, with 10 to 20 attacks per day not uncommon. After discovering early in their experience that these patients did not tolerate a depth of general anesthesia to permit endotracheal intubation, they thereafter intubated these patients with topical anesthesia, induced very light general anesthesia with a small dose of pentothal, and maintained them on nitrous oxide and oxygen supplemented with intravenous morphine or small amounts of ether. Systolic arterial pressure was kept higher than 100 mm Hg with phenylephrine if needed. Continuous ECG monitoring by oscilloscope and recorder was employed with a cardiologist present, and two 15-gauge intravenous needles were placed. The radial artery was surgically exposed, not for monitoring but to use if needed to withdraw blood to treat extreme hypertension during aortic cross-clamping or to give intraarterial transfusion in the case of catastrophic hemorrage. Blood transfusion replaced blood loss (average, 800 mL), and an electrical defibrillator was always available. The arterial pressure, measured by auscultation in the upper extremities, did not rise as much as anticipated (and in some not at all) with aortic cross-clampingbut we can imagine what the left ventricle would have looked like with TEE monitoring!. There were nine hospital deaths (20%); three patients died during surgery from cardiac arrest or ventricular fibrillation before, during, or after valve insertion, and four died suddenly 5 to 9 days postoperatively after an apparently uncomplicated recovery.

Little has been written about the anesthesia used in the early cases of direct-vision open heart surgery with moderate surface-induced hypothermia. Lewis (104) indicated that anesthesia was induced with pentothal and curare, patients were intubated, and ECG and rectal temperature were monitored. Swan (105) indicated that anesthesia was also induced with pentothal and maintained with cyclopropane and ether, or with ether alone. Robert W. Virtue with Henry Swan in Denver amplified a little on anesthetic management in their 1955 report of their first 100 cases done under hypothermia (265). Monitoring apparently included ECG, electroencephalography (EEG), blood pressure by auscultation (although this was not measured in 12% of cases and could not be obtained in one third of patients cooled to less than 35°C, and in two thirds by 33° to 31°C). Patients were given an "ordinary" anesthesia. Ether was the preferred agent ("second plane, third stage"), supplemented with curare. Virtue and Swan suggested that anesthetizing these patients was a "two-man job," with one anesthesiologist devoting full attention to maintenance of hyperventilation to deliberately achieve a respiratory alkalosis, which they believed reduced the incidence of ventricular fibrillation. [They measured right atrial pH (at the patient's temperature) just before arrest and aimed for it to be greater than 7.5alpha-stat management!]. Two plastic cannulas were placed in arm veins, and all blood loss was replaced with at least equal amounts of blood. After arrest, 100% oxygen was administered, with nitrous oxide (50%) added if needed. Patients were extubated when they were breathing adequately, apparently often before they awakened. Ventricular fibrillation occurred in 15%, and although two thirds were resuscitated, only 20% survived; in comparison, six of the seven patients who experienced cardiac arrest survived. Postoperative hemorragic shock (compared with cardiac failure) posed a difficult diagnostic problem. Average duration of circulatory arrest was 5 minutes (range, 2 to 10 minutes). Only 1 (3%) of 36 patients with favorable lesions (e.g., secundum ASD, isolated pulmonary valvular or infundibular stenosis) died, whereas 6 (75%) of the 8 with primum ASD or VSD died. Eight of ten patients with tetralogy (undergoing only relief of their pulmonary stenosis) survived.

In 1957 B.A. Sellick in London (266), and in 1959 A.W. Conn et al. at the Hospital for Sick Children in Toronto (267), reviewed their anesthetic techniques for direct-vision open heart surgery using only hypothermia in detail. Sellick used nitrous oxide with oxygen plus ether and complete relaxation with curare after pentothal and succinylcholine for induction and intubation; Conn et al. used the same agents but without muscle relaxation except for intubation. By 1959 Conn had switched to using halothane. In the paper by Conn et al., a detailed section on monitoring appeared for the first time. Monitoring included a multichannel recorder and oscilloscope, ECG and EEG, and the availability of transducers for direct pressure monitoring, although blood pressure was usually monitored with a Collens oscillometer. They report flooding the surgical field with carbon dioxide to minimize the risk of air embolization. Neither Sellick's nor Conn's group had a single death in their 32 and 63 patients, respectively!

Anesthesia for early cardiac surgery using cardiopulmonary bypass

Few details are known concerning the anesthesia provided for John Gibbon's early cases using CPB. In the dictated operative note about his one successful operation on May 6, 1953, Dr. Gibbon only mentioned that the patient was anesthetized with intravenous pentothal with an endotracheal tube and manual assistance to ventilation. Direct blood pressure readings were made via a needle inserted in the right brachial artery that was connected to a mercury manometer. The veins in both ankles were cannulated for administration of intravenous fluids. The patient was quite light at the conclusion of the operation and 1 hour later, when returned to her bed in the hospital ward, was awake, recognizing people, and talking (106). According to Anthony Dobell, who was a surgery resident under Dr. Gibbon at that time (and subsequently became chief of cardiac surgery at the Royal Victoria Hospital in Montreal), "A major factor in the deaths of the children was poor ventilation prior to going on cardiopulmonry bypass. There were no physician anesthesiologists at Jefferson at that time and of course mechanical ventilators had not been developed. Some of the children were already moribund by the time they were connected to the heart-lung machine. Thus at Jefferson, lack of expertise in anesthesia, pediatric cardiology and cardiac pathology all played a part in the initial failures" (10).

For Lillehei's early cases of open heart surgery using controlled cross-circulation, anesthesia in the patients was induced with nitrous oxide/cyclopropane and then maintained with pentothal and curare; anesthesia in donors was induced and maintained with pentothal and curare. During CPB, the donors were hyperventilated (two to three times normal values) to induce a respiratory alkalosis and counterbalance the metabolic acidosis that regularly occurred during the low-flow (34 to 40 mL/kg/minute) perfusion of the patient. No mention of monitoring, invasive lines, nor fluid management other than blood administration was made. In the first eight patients who underwent closure of VSDs (5 months to 5 years of age), the average time on CPB was 14 minutes (range, 9 to 28 minutes)! Six patients survived (31). According to Arens, Fred van Bergen and Joe Buckley administered anesthesia to the patient while Jim Matthews and Earl Schultz cared for the father donor for the first successful case (215).

In 1956, just at the time when extracorporeal perfusion was being introduced, Kenneth K. Keown of Hahnemann Medical College, who provided anesthesia for Dr. Bailey, published the first textbook, Anesthesia for Surgery of the Heart (223), that provided an insight into the nature of cardiac anesthesia in that era. As a testimony of the teamwork that had developed between cardiac surgeons and cardiac anesthesiologists, he listed the prominent teams practicing at that time (Table 1-5). He also summarized the expected mortality rates for the various procedures done at that time (Table 1-6). He emphasized the role of the anesthesiologist in ensuring that the patient was ready for surgery, the use of checklists for equipment and supplies, and the avoidance of shortcuts. Finally, he listed what he hoped would be coming in the near future: a more ideal inhalation anesthetic (potent, rapid-acting, nonirritating, nonexplosive), mechanical ventilators, arterial lines with partial oxygen pressure (PO2) and pH measurement, and a practical mechanical heart-lung machine.

Over the next 4 years, several groups reviewed their initial experience in delivering anesthesia care for patients undergoing open heart surgery with the use of mechanical heart-lung machines (224226,268,269). These reports reflected major differences of opinion regarding the optimal oxygenator, flow rates, lung management, control of arterial pressure, need to add carbon dioxide or anesthesic agents to the extracorporeal circuit during surgery, and type of monitoringitems that are still debated 40 years later! The degree of management, intervention, and monitoring ranged from the detailed protocol at the Mayo Clinic (226) to the minimalist approach at Baylor/Texas Children's Hospital in Houston (269). The former resembled modern-day practice: flows were kept at about 2.4 L/minute/m2 (60 to 200 mL/kg/minute), and ether was administered via a vaporizer on the oxygenator. Intraarterial pressure, venous pressure, rectal temperature, EEG, ECG, in-line venous saturation, and arterial blood gases were monitored. Fluid and blood balance was meticulously monitored, and a written, detailed protocol for step-by-step management was published. Vasopressor drugs and resuscitation drugs were prepared and made ready (226). At the other extreme was the practice in Houston (Cooley and Keats). They monitored only one lead of the ECG (and not invasive arterial pressure, venous pressure, EEG, or temperature), ran flows of 35 to 50 mL/kg/minute (adults and infants, respectively), and administered only d-tubocurarine during CPB (but with no recall observed!). However, their mean duration of CPB was only 13 minutes (269). Some attributed the amnesia to cerebral hypoperfusion (caused by low arterial carbon dioxide pressure and low flow rates) and found that patients rarely awakened during CPB without anesthesia when flows were 35 to 40 mL/kg/minute but invariably awakened with flows of 60 mL/kg/minute (a situation that was treated with small amounts of barbituates and narcotics) (224). The Mayo Clinic group observed no EEG changes during their high-flow CPB (226), whereas the University of Minnesota group observed severely abnormal EEG changes during their low-flow CPB (268), although no gross neurologic abnormalities were noted afterward. However, their CPB times were also usually very short (average, 14 minutes; range, 8 to 17 for the first seven cases) (114). All favored using minimal possible anesthesia and expected patients to be awake and extubated at the end of the case.

Halothane was first introduced into anesthesia practice in 1957, but there was initial hesitation to use it for cardiac surgery because of concern about its myocardial and respiratory effects. However, the desire to use a potent nonexplosive agent led the groups at Mayo Clinic (270) and Indiana University (271) to explore the use of low concentrations (less than 0.8% to 1.0%) in 50% nitrous oxide for adults and children undergoing open and closed cardiac surgery; they found halothane to be entirely satisfactory. Thereafter, this agent rapidly replaced most others and became the agent of choice for much cardiac surgery until the landmark article by Edward Lowenstein and colleagues at the Massachusetts General Hospital in 1969 (230). Lowenstein et al. indicated that they had used high-dose morphine (0.5 to 3 mg/kg) as the main anesthetic in 1,100 patients because it was devoid of myocardial depression and they considered it to be the agent of choice in patients with minimal cardiac reserve (e.g., end-stage valvular and coronary artery disease). This approach was rapidly adopted by others, and the combination of high-dose narcotics with oxygen and muscle relaxant came to be known as the "cardiac anesthetic." Mainly morphine was used for the next 10 years, until it was replaced by the synthetic narcotics, initially fentanyl in doses of 50 to 100 g/kg, as popularized in the United States by Theodore H. Stanley of the University of Utah (234). Fentanyl overcame some of the limitations of high-dose morphine, including vasodilation and the need for blood volume expansion.

Anesthesia for coronary artery surgery

In 1967 J. Earl Wynands of Montreal published the first article on the anesthetic management of patients with coronary artery disease undergoing revascularization (Vineberg procedure) (229). This was followed by an article by John F. Viljoen of the Cleveland Clinic, based on his group's experience with 1,500 IMA implant procedures (272). Both authors emphasized the desirability of generous premedication, adequate depth of anesthesia, invasive monitoring of arterial and central venous pressure, frequent measurements of arterial blood gases and serum potassium, and postoperative endotracheal ventilation with adequate analgesia and sedation for 4 to 24 hours and close cardiovascular surveillance in the intensive care unit. Wynands emphasized the importance of maintaining arterial pressures close to baseline and keeping the hematocrit at about 40 percent. In 1970, Wynands reported a hospital mortality rate of only 1.3% in their last 78 patients, despite the fact that one third had angina at rest (273)! Donald Effler, the chief of cardiac surgery at the Cleveland Clinic, attributed much of the improved results to anesthetic management (274). Viljoen advocated intermittent administration of nitroglycerine intramuscularly (272), and in 1976 Joel Kaplan, then at Emory University, introduced the use of nitroglycerine infusions during coronary artery disease (233).

Recognizing the importance of integrating cardiology into the practice of anesthesiology, a symposium on this topic, edited by Arthur Keats, was published in the August 1970 issue of Anesthesiology (275).

The 1980s

An article by Allen Ream and colleagues at Stanford in 1982 led to a rethinking of the proper management of PCO2 and pH during hypothermic CPB (197) and a near-complete shift from pH-stat to alpha-stat management during that decade. A year later, the paper by Sebastian Reiz of Umea, Sweden, raised concern about the risk of coronary steal with isoflurane (240) and led to a flurry of experimental and clinical studies on this topic. Perhaps a more provocative and influential study appeared 2 years later when Stephen Slogoff and Arthur Keats of the Texas Heart Institute in Houston documented the frequency of intaoperative myocardial ischemia during coronary artery surgery and showed that it was associated with postoperative myocardial infarction (241). They also showed that an anesthesiologist (the infamous anesthesiologist #7) can have an impact on the incidence of this problem. This paper helped initiate the intense study of perioperative ischemia, its causes, and methods to prevent it, that continues to the present day. In 1986 another pivotal study came from the Texas Heart Institute in which Drs. Nancy Nussmeier and Slogoff demonstrated that use of high-dose thiopental (to produce isoelectric EEG; average dose, about 40 mg/kg) reduced the rate of postoperative neuropsychiatric dysfunction after open ventricle operations (242). Although the general applicability of this data has been challenged, the study certainly spurred interest in the incidence, cause, and prevention of perioperative neurologic dysfunction. In 1989, two papers occurred side by side, one again from Slogoff and Keats at the Texas Heart Institute and the other from Kenneth Tuman and colleagues at Rush-Presbyterian-St. Luke's Medical Center in Chicago, documenting in large prospective studies (more than 1,000 patients each) what cardiac anesthesiologists had been saying since 1946: that the choice of anesthetic agents does not significantly affect outcome (244,245).

Monitoring

Monitoring receives much attention in modern anesthesia practice, as evidenced by Basic Monitoring Standards and Practice Guidelines, such as those for use of PAC and TEE issued by the American Society of Anesthesiologists. However, as noted previously, in articles on cardiac anesthesia up until the mid-1950s monitoring was rarely mentioned. Obviously these anesthesiologists depended heavily on their five senses, awareness, and clinical accumen (observing, for example, the color of the skin, pupils, and conjunctivae, and keeping a finger on the pulse)behavior that the modern anesthesiologist could usefully emulate.

The first "new" monitor to be introduced was the ECG. Studies using paper recorders during adult (276) and pediatric surgery (277) were reported by cardiologists in 1939 and 1948. However, apparently ECG monitoring was not commonly practiced (278) until the advent of closed mitral commissurotomy, during which arrhythmias were a major problem and all early reports mentioned use of ECG monitoring. Initially this was accomplished with the use of ordinary diagnostic ECG machines with paper recorders, but in the early 1950s oscilloscopic monitors were introduced to facilitate continuous ECG monitoring (221,258,259). A major advance in ECG monitoring occurred in 1976, when Joel Kaplan advocated the use of the V5 lead to detect myocardial ischemia in patients with coronary artery disease (232).

In 1954, Dr. Code Smith at the Hospital for Sick Children in Toronto introduced the simple but effective esophageal stethoscope, which was particularly useful in thoracic surgery (222).

With the introduction of CPB in the mid-1950s, sphygmomanometry could no longer provide reliable arterial pressure monitoring, and the use of invasive arterial lines (at least during CPB), not only for pressure monitoring but for arterial blood gas monitoring, was introduced. Initially these were often placed in the radial artery by cutdown by the surgeon, and it was not until the late 1960s that anesthesiologists began to place these lines percutaneously. Blood gas analysis was a difficult and time-consuming process and was infrequently performed until the late 1950s, when Clark, Severinghaus, and Astrup introduced their PO2, PCO2, and pH electrodes (279). Even then, it took a few years until blood gas analysis was commonplace.

A major theme of early experiences with surgery using CPB was difficulty in assessing blood volume status and evaluating ventricular function after bypass. Soon thereafter, monitoring of venous pressure (initially from catheters placed in arm veins and external jugular veins, but then from central lines placed via the groin or arm veins or placed directly into the right atrium at time of surgery) was introduced. However, as early as 1963, the Mayo Clinic group called attention to the frequent discrepancies between central venous (right atrial) and left atrial pressure and described placing catheters directly into the left atrium to monitor function and filling of the left side of the heart (228). Subsequent authors emphasized the importance of monitoring left atrial pressure in this manner in cardiac surgical patients (280,281). The monitoring of cardiac patients was revolutionized in 1970, when Swan, Ganz, and colleagues introduce their balloon-tipped PACs (61). The cardiac surgery/anesthesia team at Massachusetts General Hospital was among the first to advocate use of the PAC in cardiac surgery (231). They also introduced percutaneous introduction of the PAC via the internal jugular vein (including use of a "finding needle"), and this rapidly became the approach of choice for most anesthesiologists. (Before this, PACs were usually introduced via the brachial vein, either percutaneoulsy or by cutdown). Joel Kaplan helped to popularize the use of the PAC during cardiac surgery (282) and emphasized its role in the early diagnosis of myocardial ischemia (237) (although the latter is now largely discounted). Not only did the PAC allow estimation of the left atrial pressure, but it also provided access to mixed venous blood for oxygen analysis. In 1972 the PAC was modified to permit the easy monitoring of cardiac output by themodilution. Although the Mayo Clinic group and a few others had monitored cardiac output and identified its prognostic importance and usefulness as a guide to therapy from the dawn of open heart surgery, cardiac output was difficult to measure and was not generally used until thermodilution via PAC became available. And although we think of mixed venous oximetry as a new idea, in 1959 the Johns Hopkins Hospital group identified mixed venous oxygen as their most useful indicator of prognosis after open heart surgery (283). Although cardiac anesthesiologists were among the first and strongest proponents of the use of the PAC, they were also among the first to point out its limitations (284) and to indicate that not all cardiac surgical patients required a PAC (285,286).

The Mayo Clinic group, from the very beginning of their experience in 1955, used EEG monitoring during CPB and advocated its value as a monitor of anesthetic depth as well as integrity of cerebral perfusion (227). Others concurred (287), but early on skepticism was raised (288,289). This debate is still unresolved 40 years later.

Transesophageal echocardiography

TEE has had a profound effect on the practice of cardiac anesthesiology in the past decade, and anesthesiologists played a key role in the introduction of this modality to the practice of cardiac medicine (290). Paul Barash of Yale was perhaps the first to apply echocardiography in anesthesiology, when he evaluated the effects of halothane on ventricular function in children using transthoracic M-mode echocardiography (291). Transesophageal Doppler was first described in 1971 and transesophageal M-mode in 1976. In 1980, Masayuki Matsumoto, Yasu Oka, and others at Albert Einstein College of Medicine in the Bronx perceived the future of TEE in cardiac anesthesia when they described the use of M-mode TEE for continuous monitoring of left ventricular function in 21 patients during cardiac surgery (236). However M-mode TEE was difficult to apply except by the extremely sophisticated clinician. Although some primitive two-dimensional TEE scanners were described between 1977 and 1980, it was not until Souquet, Schluter, and Hanrath introduced their phased array transducer system mounted on the end of a gastroscope that TEE became a practical reality (292). In the early 1980s, Peter Hanrath brought prototypes to the Mayo Clinic and the University of California in San Francisco (UCSF). A cardiology fellow from Hanrath's group in Germany, P. Kremer, joined anesthesiologists Michael Cahalan and Michael Roizen at UCSF. At the 1982 meeting of the American Society of Anesthesiology, they started the TEE "revolution" when they presented their results in monitoring cardiac and vascular surgery patients with this new TEE probe, describing its usefulness in assessing filling and function of the left ventricle, myocardial ischemia, and intracardiac air (238,239). R.F. Cucchiara and colleagues at the Mayo Clinic described its usefulness in detecting air embolism during neurosurgery (293), while the UCSF group described its superiority over ECG in detecting myocardial ischemia (294). In 1987 Cahalan et al. (295) and Clements and deBruijn at Duke University (296) wrote review articles on the use of TEE in anesthesiology. In 1986, Hewlett-Packard introduced color flow Doppler with TEE, and Norbert deBruijn and colleagues at Duke University reviewed their early experience with this new technology (243). In that same year, pulsed wave Doppler was added to TEE, and in 1989 biplane probes first became available. The Society of Cardiovascular Anesthesiologists has played a key role in the development of perioperative TEE. In conjunction with the American Society of Anesthesiologists they developed the Practice Guidelines for Perioperative TEE in 1996, and in collaboration with the American Society of Echocardiography they helped initiate the first examination in Perioperative TEE, which was administered by the National Board of Echocardiography in 1998. Today TEE is one of the defining characteristics of a cardiac anesthesiologist.

Cardiac anesthesia becomes a subspecialty

It is difficult to identify a precise time when cardiac anesthesia became a subspecialityin a sense it began with Harmel and Lamont's care of Dr. Blalock's blue babies in late 1944, which led to the first paper on cardiac anesthesia in 1946 (218), or with the publishing of the first textbook on cardiac anesthesia by Keown in 1956 (223). Some could argue that because the subspeciality is not recognized by the American Board of Anesthesiology, nor by the American Board of Medical Specialties, it is not a subspecialty; but most accept its subspecialty status. This is because of the special knowledge, skills, and activities required of anesthesiologists who attend these patients. In the beginning, these aspects consisted of intimate knowledge of the pathophysiology of congenital heart disease and how various anesthetic techniques interact with this pathophysiology (254). Later was added the pathophysiology of valvular heart disease, and finally that of coronary artery disease (273). Next was required knowledge of the entirely new techniques that surgeons used to manage these patients: initially hypothermia, then CPB and all of its nuances including deep hypothermic circulatory arrest, coronary perfusion, cardioplegia, and retrograde cerebral perfusion. In recent years this has included minimally invasive techniques such as Port Access System. "Advanced" monitoring techniques, not usually used in noncardiac anesthesia at the time they were introduced, were on the list of new skills and knowledge required of the cardiac anesthesiologist. These included ECG, EEG, arterial lines, and central venous and left atrial pressure monitoring; next the PAC; and most recently, TEE. Intimate knowledge of blood coagulation and anticoagulation and the administration of blood products (often in large quantities) and of various drugs used to modify coagulation was required. Finally, a thorough understanding of the pathophysiology of abnormal hemodynamic states and manipulation with potent and often novel hemodynamically active agents and mechanical assist devices was required. [In briefly reviewing some of the knowledge and techniques first introduced into and unique to the practice of cardiac anesthesia, it is apparent that much of this was eventually transferred and adopted into the general practice of noncardiac anesthesia].

To gain all of this knowledge and skill, residents began to seek special training (fellowships) in cardiac anesthesia in the 1970s. Programs at Massachusetts General Hospital, Emory University, University of Alabama, Texas Heart Institute, and the Cleveland Clinic, to name only a few, were important "incubators" for future cardiac anesthesiologists. Also, modern encyclopedic textbooks on cardiac anesthesia began to appear, starting with the classic text edited by Joel Kaplan in 1979 (235), and cardiac anesthesiologists began to meet together to share their experience, ideas, and problems. In 1972, the Association of Cardiac Anesthesiologists was founded with B. Dalton as president, Emerson Moffitt as vice president, and Edward Lowenstein as secretary (215). Because this organization limited its membership to 50, in 1978 the Society of Cardiovascular Anesthesiologists was established (Table 1-7) and quickly became a leading society in the entire specialty of anesthesiology, not to mention the subspecialty. In 1987, a new journal appeared devoted to the subspecialty, the Journal of Cardiothoracic Anesthesia.

Another somewhat unique characteristic of the subspecialty of cardiac anesthesia was the concept of a team. Brock spoke of this in his previously mentioned lecture in 1949 (212), and Keown listed such teams in 1956 (Table 1-5) (223). The surgeon was no longer able to oversee the whole procedure. Dodds, in his 1961 paper (297), emphasized the role of the anaesthetist in caring for the patient and overseeing perfusion during CPB so that the surgeon could concentrate on the problems involved in correcting the cardiac defects. Cardiac anesthesiologists also continued to care for these patients in the early postoperative period, and cardiac surgery and cardiac anesthesia played important roles in the development of surgical intensive care units (248), and conversely in transferring the practices of intensive care into the operating room.

Although many played invaluable roles in the development of cardiac anesthesia into a subspecialty, it is my personal opinion that much of the credit for the popularity and status of this subspecialty should go to Joel E. Kaplan (originally at Emory University, then Chair of Anesthesiology at Mount Sinai School of Medicine in New York, and now Dean of the School of Medicine in Louisville). He "sold" the importance and value of cardiac anesthesiologists to surgeons and anesthesiologists at various meetings. The textbook he edited, which was first published in 1979, thoroughly catalogued and covered the knowledge and technical aspects needed and set a standard against which all other texts would be measured. His name almost became synonymous with the PAC (see, for example, the logo on the fourth edition of his textbook and on the journal he edits). He helped introduce intravenous nitroglycerin infusions and monitoring of the V5 lead to the specialty. In 1987 he started the first journal devoted to cardiac anesthesia. He was the fourth president of the Society of Cardiovascular Anesthesiologists (19831985) and, in recognition of his knowledge and skills as a communicator, gave a refresher course lecture on cardiac anesthesia for more than 10 years at the Annual Meeting of the American Society of Anesthesiologists.

Maturation of the subspecialty

The last two decades have witnessed remarkable growth of our subspecialty in terms of prominence and scientific contributions. Many cardiac anesthesiologists have became chairs of anesthesia departments and a few have been deans or higher officials in various academic centers. Cardiac anesthesiologists play active roles in the Society of Thoracic Surgeons (e.g., leading workshops on neurologic consequences of cardiac surgery), the American Society of Echocardiography, and the American College of Cardiology/American Heart Association (e.g., committee to develop guidelines for perioperative cardiovascular evaluation for noncardiac surgery); serve as associate editors of major anesthesia journals; help produce and edit two modern textbooks on CPB; and organize and direct major annual workshops on CPB and TEE.

Major research contributions have been made and continue to be added in such diverse areas as the pathophysiology of CPB including the systemic inflammation response, neurologic consequences of cardiac surgery, alpha-stat versus pH-stat blood gas management during hypothermia, perioperative myocardial ischemia, molecular cardiovascular medicine, deep hypothermia with or without circulatory arrest in both adults and children, retrograde cerebral perfusion, evaluations of new cardiovascular and anesthetic drugs, changes in coagulation associated with CPB including its monitoring and modulation with drugs, and the application and improvement of information provided by TEE. Cardiac anesthesiologists have made important contributions in the areas of risk assessment (e.g., Higgins) and outcome research (e.g., Mangano and Fleisher). Mangano has been instrumental in initiating large multicenter collaborative research projects (e.g., McSPI) to study outcome and assess methods of improving outcomes in cardiac surgery. Reves, Murkin, Newman, and many others have pioneered in the objective assessment of neurologic effects of CPB. Moffitt elevated to a new level the study of the effects of various anesthetic agents on myocardial ischemia using coronary sinus flow catheters. Cheng has provided objective data on the cost-effectiveness of fast tracking and early extubation. [Interestingly Barash et al. had advocated early extubation as long ago as 1980 (298)].

Finally, cardiac anesthesiologists have been responsive by developing techniques that facilitate new procedures in cardiac surgery, such as minimal access surgery, transmyocardial laser, the Batista operation, valve repair and use of stentless valves, more aggressive neonatal surgery, and fast-tracking.

Several authors have examined the nature of discovery as it applies to medicine in general and to cardiothoracic surgery in particular (125,145,299302). Comroe's monograph, Retrospectroscope: Insights into Medical Discovery (299), is particularly illuminating. Gott identified four common attributes of the great innovators in cardiac surgery: brilliance, determination, creativity, and courage (10). However, when one mentions courage on the part of a surgeon, one must concur with Westaby's comment after reviewing the course of Barney Miller, the first patient to receive a Javik artificial heart: "We should remember that without the consent of many courageous patients, the great advances [in cardiac surgery] could not occur" (12).

One of the phenomena frequently noted was the near-simultaneous accomplishment of a new procedure. Crafoord's first coarctation repair was in October 1944, Gross' in July 1945. Sellors' first closed pulmonary valvotomy was in December 1947, while Brock's occurred in February 1948. Bailey's first successful mitral commissurotomy was on June 10, 1948, while Harken's was on June 16. [The latter, on hearing of Bailey's earlier success, rushed to get his case published before Bailey's and was successful in doing so (100).] Smithy had done several mitral valve operations earlier that same year, and Brock did his first case in September. Lewis' first successful closure of an ASD using hypothermia was in September 1952, while Swan did an open pulmonary valvotomy using similar techniques in February of 1953. Kirklin conducted the first series of successful open heart operations with a mechanical heart-lung machine between March and May 1955, while Lillehei, who had been using cross-circulation up until that time, began his series of open heart surgery with a mechanical heart-lung machine between May and August of 1955. Ross first inserted a subcoronary aortic homograft valve in July 1962, and Barratt-Boyes did so in August of the same year. Jateen did the first successful arterial switch operation for TGA in Sao Paulo in May of 1975, and Yacoub did his first in London in October. Some of these surgeons were aware of the others' work, and competition may have played a role. But also it seems that sometimes the time is right for a new procedure to appear. All the pieces of the puzzle are ready to be assembled by the adventuresome, competent, and eager surgeon.

There are a number of relevant observations to be made from a review of the history of cardiac surgery and anesthesiology.

Serendipity often comes into play. Examples include the discovery of heparin [McLean was looking for a coagulant (49,50)], protamine reversal of heparin [Chargoff and Olson were trying to prolong the action of heaparin (51)], selective coronary angiography (Sones was performing an aortic root arteriogram when the catheter inadvertently slipped into the coronary arteryand the patient didn't die!), closed chest massage (Kowenhoven and Jude noted a pressure rise when the defibrillator paddles were applied), and aprotinin (while trying to block the inflammatory response to CPB, the investigators noted that the surgical fields were surprisingly dry).

There is often a thin line between success and failure. Strieder might have accomplished the first successful ductus closure had not his patient died of sudden gastric aspiration 5 days after surgery, and Merendino might have accomplished the first successful correction of TGA had not his patient suddenly died of an apparent cerebral air embolism several hours postoperatively.

Beware of rejecting new ideas and the danger of "conventional wisdom." The early rejection of Brunton's and Souttar's proposal and success with mitral commissurotomy, rejection of Kolessov's and Green's IMA-coronary artery anastomosis, and Gross' rejection of Taussig's proposal to create an artificial ductus are examples.

Perserverance is important. Charles Bailey persisted for 3 years before he achieved a successful mitral commissurotomy. Mustard devoted 10 years to conquering TGA. Vineberg demonstrated the validity of his operation in the laboratory in 1946 and performed the operation clinically and published his results throughout the 1950s, but it was not until Sones demonstrated function of these implants in the early 1960s that Vineberg's work was accepted. Most impressively, John Gibbon pursued his quest for 23 years until he solved the challenge of CPB.

Do not get discouraged if you do not get to train where you want to. Helen Taussig was rejected for an internship at Johns Hopkins, and Alfred Blalock was rejected for a chief residency by the same institution. (The institution then had the wisdom to bring both of them back on its faculty.)

Youth does not preclude innovative success and in fact tends to encourage it. McLean was a medical student when he discovered heparin (49,50), and Gross was a surgery resident when he first successfully ligated a PDA. Gibbon constructed his first successful heart-lung machine while still in training. Kirklin, Lillehei, and Starr were in their mid-thirties and barely out of their training when they started making their monumental contributions. [Conversely, Lowell Edwards and William Kouwenhoven were retired engineers when they made their important contributions].

Laboratory work is important in providing a foundation for clinical success. Most of the great clinical advances, such as ligation of PDA, resection of coarctation, creation of the subclavian-to-pulmonary artery shunt, IMA implantation, and artificial valves, were preceded by extensive laboratory investigation. Further, as pointed out by Comroe, many of these clinical advances were dependent on basic science research, much of which had no apparent practical application at the time that it was performed (125).

Interaction with those in other disciplines and other countries is also important. Wheat's application of antiadrinergic therapy for aortic dissection was inspired by communication with pharmacologists and veterinary science specialists. Dillard's and Barratt-Boyes' development of techniques for deep hypothermic circulatory arrest arose from input from surgeon-scientists from Japan who were working in their units.

Competetion can spur successwitness Crafoord and Gross, Harken and Bailey, Swan and Lewis, and Kirklin and Lillehei.

A creative environment stimulates success. The Johns Hopkins Hospital under Alfred Blalock was an early example. From this environment also came Bahnson, Cooley, McGoon, Sabistan, and Spencer. Another dramatic example is the University of Minnesota in the early 1950s under the leadership of its chairman of surgery, Owen Wangensteen. In that environment over the course of 5 years, Dennis attempted the first open heart surgery using a heart-lung machine, Lewis first closed an ASD with hypothermia, Lillehei introduced cross-circulation and with it first successfully closed a VSD and repaired a tetralogy of Fallot, Campbell successfully used a biologic (dog lung) oxygenator, and DeWall introduced his bubble oxygenator. Trainees at the University of Minnesota at that time included Barnard, Shumway, and Gott (303). A similarly productive environment was subsequently established by Shumway at Stanford with its impressive research and clinical program in heart transplantation.

Consider reexamining the staus quo, the "standard of care"examples include hypothermia, cold cardioplegia, and prolonged intubation.

Reassess but don't necessarily abandon a sound procedure because of early failure. After his first five attempts at correction of tetralogy failed, Kirklin waited a year and tried again, this time with 80% success. Harken and Brock almost quit doing mitral commissurotomies when they had a series of early deaths, but immediately thereafter almost all of their patients survived. Four of Starr's first five aortic valve replacement patients died. After the prosthesis was modified, nine of the next ten survived.

Finally, we all "stand on the shoulders of giants."

Lest we become overly impressed with the accomplishments and outcome with current cardiac surgery and anesthesia, some of the remarkably good results of our predecessors should be recalled. In their 1956 report of their first 1,000 cases of surgery for congenital heart disease at Chicago's Memorial Children's Hospital, Potts and McQuiston (surgeon and anesthesiologist, respectively) reported no deaths among 347 children (age 28 days to 16 years) undergoing closure of a PDA (257). In 1959 Conn reported 63 consecutive secundum ASDs closed with the aid of hypothermia and inflow occlusion at the Hospital for Sick Children in Toronto without a fatality (267). In 1970 Wynands reported only 1 death in their last 78 patients undergoing a Vineberg procedure in Montreal, even though one third had rest angina and this operation did not result in immediate improvement in coronary perfusion (273). But perhaps most striking of all was the report by Dwight McGoon and Emerson Moffitt, respectively surgeon and anesthesiologist at the Mayo Clinic, of their first 100 aortic valve replacements with a Starr-Edwards valve, done between February 1993 and December 1994 with no deaths (130). This was of course before the availability of CABG, cardioplegia, PACs, and TEEand the patients were usually extubated in the operating room!

In closing this brief history of cardiac surgery and anesthesia, if we wonder what it has all been about, we need only listen to Lord Brock: "These operations . . . are tiring and anxious procedures involving much care, responsibility and hard work. Fortunately they have their happier side and we are in large part recompensated for the long and difficult hours by seeing the almost miraculous change in the children themselves and in witnessing the joy and relief of the parents when they see their children running about happily and without effort like other children" (212). The modern anesthesiologist is perhaps jaded by daily miracles that go unrecognized. To really appreciate what the cardiac anesthesiologist does, it may be necessary to have been a physician, as Lord Brock was 4 years before he made the statement quoted, when medicine and surgery had nothing to offer most patients with heart disease. And if we are content with what we are able to do today and accept some obstacles as unsolvable, let us contemplate the closing paragraph in Kirklin's article on the occasion of the 25th anniversary of open heart surgery at the Mayo Clinic: "We could, of course. . . . rejoice in our accomplishments, and accept the idea that nature sets certain limits to everything, including cardiac surgery. Billroth expressed such a view in 1897 when he said that cardiac surgery had reached the limits set by nature. Those in 1954 who urged aborting the pump-oxygenator effort must have had a similar notion. Not the passage of time but the efforts of many people have proven the idea to be wrong at both points in time. I believe that acceptance of such an idea today would also be wrong" (113).

The author gratefully acknowledges the opportunities, challenges, and inspiration provided to him by Drs. K. Alvin Merendino and Thomas F. Hornbein of the University of Washington and Dr. Fawzy G. Estafanous of the Cleveland Clinic.

Liss RS. The history of heart surgery in the United States (19381960).Zurich:Juris Druck + Verlag, 1967.

Johnson SL. The history of cardiac surgery 18961955. Baltimore: The Johns Hopkins University Press, 1970.

Clowes GHA. The historical development of the surgical treatment of heart disease: Symposium on the Heart, American Association for the History of Medicine 32nd Annual Meeting, May 22, 1959.New York: Plenum Press, 1960.

Baird RJ. "Give us the tools.. . . " The story of heparinas told by sketches from the likes of William Howell, Jay McLean, Charles Best and Gordon Murray.
J Vasc Surg
1990;11:4.

Chargaff E, Olson KB. Studies on the chemistry of blood coagulation: IV. Studies on the action of heparin and other anticoagulants: the influence of protamine on the anticoagulant effect in vitro.
J Biol Chem
1937;122:153.

Harken DE. Foreign bodies in, and in relation to the thoracic blood vessels and heart:I. Techniques for approaching and removing foreign bodies from the chambers of the heart.
Surg Gynecol Obstet
1946;83:117.